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Vitamins and Nutrients as Primary Treatments in Experimental Brain Injury: Clinical Implications for Nutraceutical Therapies

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... In the pathophysiology of TBI, increased production of free radicals and reactive oxygen species after injury leads to oxidative stress and secondary neurotoxicity (7). In cases where there is a deficiency of various antioxidants, involved in recovery of brain tissue post injury, treatment with antioxidants may be theoretically effective in preventing propagation of tissue damage as well as in improving short-and long-term survival/functional outcomes (8)(9)(10)(11)(12). Several animal studies have evaluated that vitamin E supplementation before TBI reduced oxidative stress and improved learning and memory (13,14). ...
... Reactive oxygen species-induced oxidative damage has been identified as a major contributor to secondary injury from TBI, which has resulted in further damage to neuronal tissue and vasculature. Therefore, various antioxidants such as vitamin B, C, D, zinc, and magnesium have been used before and after TBI to prevent further brain damage (8,10). Among them, vitamin E has been highlighted because it can easily be implemented in emergency care. ...
... Vitamin E is also known as one of the factors inhibiting genetically programmed cell death, and has been used in studies to treat degenerative brain diseases (30). Vitamin E depletion is one of the major factors that increase vulnerability to TBI (8,9). ...
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Background Traumatic brain injury (TBI) is a major public health problem with high mortality and disability. Vitamin E, one of the antioxidants for treatment of TBI, has not been sufficiently evaluated for predicting prognosis of TBI. This study aimed to evaluate the prognostic value of vitamin E on functional outcomes of TBI patients with intracranial injury. Methods A multi-center prospective cohort study was conducted in five university hospitals between 2018 and 2020. Adult TBI patients who visited the emergency department (ED) with intracranial hemorrhage or diffuse axonal injury confirmed by radiological examination were eligible. Serum vitamin E levels (mg/dL) were categorized into 4 groups: low (0.0–5.4), low-normal (5.5–10.9), high-normal (11.0–16.9), and high (17.0–). Study outcomes were set as 1- and 6-month disability (Glasgow outcome scale (GOS) 1–4). Multilevel logistic regression analysis was conducted to calculate the adjusted odds ratios (AORs) of vitamin E for related outcomes. Results Among 550 eligible TBI patients with intracranial injury, the median (IQR) of serum vitamin E was 10.0 (8.0–12.3) mg/dL; 204/550 (37.1%) had 1-month disability and 197/544 (36.1%) had 6-month disability of GOS 1–4. Compared with the high-normal group, the odds of 1-month disability and 6-month disability increased in the low and low-normal group (AORs (95% CIs): 3.66 (1.62–8.27) and 2.60 (1.15–5.85) for the low group and 1.63 (1.08–2.48) and 1.60 (1.04–2.43) for the low-normal group, respectively). Conclusion Low serum vitamin E level was associated with poor prognosis at 1 and 6 months after TBI with intracranial injury.
... Micronutrients have been shown to have a variety of mechanisms and overall low toxicity, making them an attractive candidate for supplemental therapies in patients with neurologic injury [52]. While beyond the scope of this review, researchers have previously summarized outcomes associated with micronutrient delivery among the neurologically impaired population ( Table 2). ...
... Although those receiving the immune-enhancing formula were found to have a concurrent reduction in serum IL-6 and rise in glutathione compared to control, morbidity, and mortality outcomes were not reported. Fatty acids, specifically n-3 PUFAs including DHA and EPA, have shown promising results in preclinical studies [52], though translation to clinical research is limited. Theoretic benefits include a reduction in inflammatory and oxidative responses, antithrombotic effects, and improved maintenance of tissue micro perfusion [50,52]. ...
... Fatty acids, specifically n-3 PUFAs including DHA and EPA, have shown promising results in preclinical studies [52], though translation to clinical research is limited. Theoretic benefits include a reduction in inflammatory and oxidative responses, antithrombotic effects, and improved maintenance of tissue micro perfusion [50,52]. The effect of daily administration of n-3 supplementation (via EPA, mixed EPA/DHA, and EN containing EPA/DHA) during the vasospasm window following SAH has been found to have significantly fewer occurrences of vasospasm [60,61], infarcts [61], and more favorable outcomes [60]. ...
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Purpose of Review This review presents the most current recommendations for providing nutrition to the neurocritical care population. This includes updates on initiation of feeding, immunonutrition, and metabolic substrates including ketogenic diet, cerebral microdialysis (CMD) monitoring, and the microbiome. Recent Findings Little evidence exists to support differences in feeding practices among the neurocritical care population. New areas of interest with limited data include use of immunonutrition, pre/probiotics for microbiome manipulation, ketogenic diet, and use of CMD catheters for substrate utilization monitoring. Summary Acute neurologic injury incites a cascade of adrenergic and neuroendocrine events resulting in a pro-inflammatory and hypercatabolic state, which is associated with an increase in morbidity and mortality. Nutritional support provides substrates to mitigate the damaging effects of hypermetabolism. Despite this practice, studies on feeding delivery outcomes remain inconsistent. Guidelines suggest use of early enteral nutrition using standard polymeric formulas. Population heterogeneity, variability in interventions, complexities of the metabolic and inflammatory responses, and paucity of nutrition research in patients requiring neurocritical care have led to controversies in the field. It is imperative that more pragmatic and reproducible research be conducted to better understand underlying pathophysiology and develop interventions that may improve outcomes.
... The present review summarizes the preclinical in vivo studies and the few available human clinical studies in which nutritional interventions were applied as prophylaxis before the HI cerebral damage, either as a maternal dietary supplementation during pregnancy or to the offspring before HI induction. The interventions examined only included natural products and nutraceuticals, which may be attractive alternatives to traditional drugs as they have a low toxicity profile, are comparatively affordable, and are widely available [38][39][40]. The neuroprotective and preventive properties of polyphenols, omega-3 fatty acids, vitamins, and other plant-derived and endogenous compounds in the context of neonatal HI are summarized below. ...
... Vitamins are organic molecules needed for normal physiological functioning that are emerging as potential primary therapeutics [38]. Vitamins have been largely researched for their roles as essential nutrients in physiology, but recently, research has begun to examine how they are involved in nervous system dysfunction, from chronic diseases to acute insults like HI. ...
... Moreover, in another study of vitamin E using a rat model of HI, 1.5 mg of α-tocopherol acetate was administered via subcutaneous injection to female pups at P4, P6, and P8, with HI induction at P7. Vitamin E treatment prevented the effects of HI damage on oxidative stress and inflammation markers, including the inducible and neuronal nitric oxide synthases (iNOS and nNOS) and some insulin-growth-factor-related proteins [70]. While vitamin E has high lipid solubility and low toxicity, it takes a considerable amount of time to reach effective levels in the CNS and can cause hemorrhage at very high doses [38]. These limitations should be considered when considering vitamin E as a potential neuroprotectant. ...
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Neonatal hypoxia–ischemia (HI) is a brain injury caused by oxygen deprivation to the brain due to birth asphyxia or reduced cerebral blood perfusion, and it often leads to lifelong limiting sequelae such as cerebral palsy, seizures, or mental retardation. HI remains one of the leading causes of neonatal mortality and morbidity worldwide, and current therapies are limited. Hypothermia has been successful in reducing mortality and some disabilities, but it is only applied to a subset of newborns that meet strict inclusion criteria. Given the unpredictable nature of the obstetric complications that contribute to neonatal HI, prophylactic treatments that prevent, rather than rescue, HI brain injury are emerging as a therapeutic alternative. Nutraceuticals are natural compounds present in the diet or used as dietary supplements that have antioxidant, anti-inflammatory, or antiapoptotic properties. This review summarizes the preclinical in vivo studies, mostly conducted on rodent models, that have investigated the neuroprotective properties of nutraceuticals in preventing and reducing HI-induced brain damage and cognitive impairments. The natural products reviewed include polyphenols, omega-3 fatty acids, vitamins, plant-derived compounds (tanshinones, sulforaphane, and capsaicin), and endogenous compounds (melatonin, carnitine, creatine, and lactate). These nutraceuticals were administered before the damage occurred, either to the mothers as a dietary supplement during pregnancy and/or lactation or to the pups prior to HI induction. To date, very few of these nutritional interventions have been investigated in humans, but we refer to those that have been successful in reducing ischemic stroke in adults. Overall, there is a robust body of preclinical evidence that supports the neuroprotective properties of nutraceuticals, and these may represent a safe and inexpensive nutritional strategy for the prevention of neonatal HI encephalopathy.
... Concussion is induced by force transmitted to head resulting from direct or indirect injury to head, face, or elsewhere and presents with a range of clinical symptoms, including physical signs, behavioral changes, cognitive impairment, somatic symptoms, often presents with rapid onset and resolve spontaneously; the pathogenic mechanisms of long-term consequences after traumatic brain injuries are still unclear and combination of different alterations such as excitotoxicity, blood flow, free radical damage (oxidative stress), disrupted regional metabolic processes has been identified as major contributors to the secondary damage after mild brain injuries [3,4,5,6]. Concussion results in pathological changes at ultrastructural level, which initiate neurochemical and neurometabolic cascades, including disruption of neurofilaments and hyperglycolysis associated with oxidative dysfunction [5,7,8]. Some authors have shown that secondary damage after mild brain injury leads to failure in adenosine triphosphate synthesis and increases of reactive oxygen in species [4]. ...
... Some authors have shown that secondary damage after mild brain injury leads to failure in adenosine triphosphate synthesis and increases of reactive oxygen in species [4]. In animal models it was shown that mTBI alters brain functions for hours to years in a variety of different pathological syndromes, including increase of glucose metabolism, which also may persist for up to four weeks after injury [3,5,7,8,9]. These dysmetabolic processes that follow concussion are associated with oxidative stress and are reversible in many cases of damaged brain cells, however, some cells may die [3,6]. ...
... In many studies, various vitamins data have been explored with the regards to experimental brain injury [8,10,11]. Some authors have reported changes in vitamin status observed in the patients with mTBI [12]. ...
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Introduction. Mild traumatic brain injury (mTBI) was reported to be the most frequent among other types of brain injuries and is the main reason for the disability in mid-life and middleaged people. It’s known that antioxidants can reduce oxidative stress, so, to prevent secondary brain injury modulating maintaining of long-term consequences after mTBI. Purpose of the study. This work was to study the serum vitamin E, C and A levels in the patients with long-term consequences after mTBI to explore their potential pathogenetic influence. Materials and methods. Sixty-seven patients with long-term consequences after mTBI were investigated with the mean age of 43,61 ± 8,24 years (18 women, 26,86% and 49 men, 73,14%) where the vitamin E, C and A contents were measured in sera by spectrophotometer method using standard protocols and reagents (Sigma, USA). Results. In this work, it was found descending serum levels of all investigated vitaminantioxidants in almost all patients with longterm consequences after mTBI where the content of vitamins A (M ± s: 1,63 ± 1,56 mkM/l) and E (25,41 ± 0,93 mkM/l) had a tendency to decreasing without significant differences compare to controls. It was found the statistically significant decreased of vitamin C levels in the serum samples of our investigated patients when compared to controls (p < 0,05, t = 4,59, 95% CI 98,81 to 55,68) where in the main patient group, the medians of total vitamin C level was 30,57 ± 5,38 mkM/l vs 36,91 ± 5,22 mkM/l in controls. It was shown that the patients with long-term consequences after mild contusion in anamnesis (64,18%) had the prominent changes in the vitamin C content. Conclusion. The maintaining of long-term consequences of mTBI was accompanied by the vitamin-antioxidant dyshomeostasis such as decreasing of vitamin C serum level associated with a tendency to decreasing of vitamins A and E levels that may play the certain role in the pathogenesis. All these data are needed to be accounted into the consideration during the treatment of this patient category.
... Vitamins are required for normal human physiology and some vitamins even participate in a variety of processes within the brain. The physiological roles of vitamins have been extensively investigated and their involvement in the regulation of nervous system dysfunction has also been reported recently [9]. Despite different chemical structures and characteristics, different vitamins share some common features. ...
... Vitamin E has prevention effects on the oxidation of phospholipids and polyunsaturated fatty acids, helps to maintain integrity of cell membrane, reduces blood lipid peroxide, prevents platelet aggregation, increases the stability of erythrocyte membrane, promotes the synthesis of red blood cells, etc. [26]. Previous studies have discovered that a-tocopherol (a-T) is one of the most biologically active forms of vitamin E and a lipid-soluble antioxidant [9,27]. After hepatic uptake, a-T can be resecreted by a-T transfer protein (a-TTP) from liver to plasma [28]. ...
... Vitamin C is a water-soluble vitamin, also known as Lascorbic acid, which is a very important scavenger for the endogenous free radical and can be neuroprotective by reducing damages from excito-toxicity [9]. The main function of vitamin C is to help human body to accomplish the REDOX reaction, thus important in preventing diseases, such as cancer, atherosclerosis, and rheumatism, as well as in enhancing immunity. ...
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Vitamins are vital to sustain normal physiological function, metabolism, and growth for all living organisms. Being an integral component of coenzyme, vitamins can affect the catalytic activities of many enzymes and the expression of drug transporters. Genetic variations in metabolism and/or transporter genes of drugs can influence the exposure of the human body to drugs and/or their active metabolites, thus contributing to the variations in drug responses and toxicities. Nonetheless, pharmacogenomics studies on nutrients have been rarely summarized. In this article, we reviewed recent progress on vitamin pharmacogenomics, for a better understanding on the influence of vitamin-related gene polymorphisms on inter-individual differences in diseases and drug efficacy and safety.
... In preclinical animal models, 41-44 nutraceuticals, bioactive compounds, and functional foods (eg, choline, resveratrol, creatine, and sulforaphane) may be promising alternatives to traditional pharmaceuticals because they have a low potential for toxicity and are broadly accessible. 45,46 Such dietary supplements provide benefits through a range of mechanisms, including enhancing reperfusion, cellular energy stores, and brain-derived neurotrophic factor, and reducing oxidative damage, inflammation, excitotoxicity, and cerebral metabolism. [45][46][47] Except for choline, this review did not find any clinical trial on these substances. ...
... 45,46 Such dietary supplements provide benefits through a range of mechanisms, including enhancing reperfusion, cellular energy stores, and brain-derived neurotrophic factor, and reducing oxidative damage, inflammation, excitotoxicity, and cerebral metabolism. [45][46][47] Except for choline, this review did not find any clinical trial on these substances. ...
Article
Context: Nutritional interventions for newborns with brain injury are scarce, and there are gaps in the knowledge of their mechanisms of action in preventing the occurrence of cerebral palsy (CP) or the incidence of other developmental disabilities. Objective: The objective of this review was to assess the effect of nutritional interventions in preventing nonprogressive congenital or perinatal brain injuries, or in improving outcomes related to neurological development. Data sources: Randomized trials on any nutritional intervention for pregnant women at risk of preterm delivery, or for children with low birth weight, preterm, or with confirmed or suspected microcephaly, CP, or fetal alcohol syndrome disorders (FASDs) were retrieved from MEDLINE, Embase, Scopus, Web of Science, LILACS, and CENTRAL databases from inception to September 17, 2020. Data extraction: Data extraction, risk of bias (Cochrane Risk of Bias tool 2), and quality of evidence (GRADE approach) were assessed by 2 authors. Data analysis: Pooled risk ratios (RRs) with 95% confidence intervals were calculated using a random-effects meta-analysis. Seventeen studies were included on intravenous interventions (magnesium sulfate [n = 5], amino acids [n = 4], vitamin A [n = 1], and N-acetylcysteine [n = 1]); enteral interventions (vitamin D [n = 1], prebiotic [n = 1], nutrient-enriched formula [n = 1], and speed of increasing milk feeds [n = 1]); and oral interventions (choline [n = 1] and docosahexaenoic acid, choline, and uridine monophosphate [n = 1]). All studies assessed CP, except 1 on FASDs. Eight studies were judged as having high risk of bias. Five studies (7413 babies) with high-quality evidence demonstrated decreased risk of childhood CP (RR = 0.68, 95% CI: 0.52-0.88) with magnesium sulfate. Interventions with amino acids had no effect on CP prevention or other outcomes. Except for 1 study, no other intervention decreased the risk of CP or FASDs. Conclusion: Although different types of nutritional interventions were found, only those with antenatal magnesium sulfate were effective in decreasing CP risk in preterm infants. Well-designed, adequately powered randomized clinical trials are required.
... The findings in some central nervous system diseases that cause neuronal damage suggested that NSE might be a specific indicator for neural damage 15 . Nutritional-based therapies can represent a significant part of combination therapies as these agents have complemented the therapeutic effect on biological function and damage to the brain in several studies 16 . Previous studies showed that supplementation of essential nutrientsfor the metabolic cascade in the early stages of injury contributes to the functional recovery of patien 4 . ...
... There are various studies on the primary damage following head trauma and neuronal degeneration resulting from its secondary damage that use nutrition-based therapies to support the healing process in the treatment of experimental brain injury in recent years 16 . The mechanism of the injury, the severity of the injury, the pathology of the lesion, the involved brain region the other hand, the NSE activity of the betaine group was lower, but this decrease was not statistically significant. ...
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Introduction: Due to irreversible damage following head trauma, many overlapping pathophysiological events occur including excitotoxicity, acidotoxicity, ionic imbalance, edema, oxidative stress inflammation and apoptosis. Material and methods: In this this study, after the rats were separated in to groups theserats were fed throughout fourteen days with betaine, omega-3 or betaine+omega-3 combination in physiological limits prior to the trauma. After a closed head trauma, the damaged brain tissues were collected for biochemically and histologically analyses. This examination involved analyses of levels of caspase-3 and cytochrome C and neuron-specific enolase (NSE) levels in brain tissue. Results: These analyses showed that traumatic brain injury (TBI) caused an increase in the levels of caspase-3, cytochrome C and neuron-specific enolase (NED) in the brain tissues examined. Discussion: In this study, apoptotic and/or necrotic cell death via mitochondrial cytochrome C caspase pathway in traumatized cells and neuron-specific enolase (NED) increase indicative of neuronal damage confirmed the research hypothesis. Conclusion: Level of the biomarkers induced by brain injury in the groups fed with betaine, omega-3 and betaine+omega-3 combination before the traumatic damage approximated to that of control group values, suggesting that these products may have a neuroprotective role. Key words: Betain, Caspase-3, Cytochrome C and Neuron-specific enolase, Omega-3, Traumatic brain injury.
... [60][61][62][63][64]. ...
Article
Rehabilitation following neurotrauma is an important component of recovery. The best outcomes involve multidisciplinary management. This involves medical therapies, functional therapies, and physical therapies. Speech therapy, physical therapy, and occupational therapy are crucial components. Emerging evidence has implicated the need for vision therapies and a focus on mental health. A seamless integration from inpatient to outpatient is validated. This can be at outpatient facilities or home care. The importance is a key point person for the patient.
... In the case of increased ROS and RNS formation, the quality of food consumed and/or supplementation of adjuvants and nutraceuticals is of fundamental importance to provide significant protection [84,85]. Despite of the link between oxidative/nitrosative damage and TBI is evident, as well as continuous growth of studies, reporting either preclinical or clinical data, using supplementation with natural or synthetic low molecular weight antioxidants, that have appeared in the literature in the last decades as potentially useful treatments in TBI, still the awareness that deficiency in antioxidant-rich foods in the daily diet may further exacerbate TBI symptoms still highly plausible [86][87][88]. ...
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Objective: To evaluate dietary adequacy of patients presenting for evaluation at an outpatient Traumatic brain injury (TBI) clinic. Research Design and Method: We identified 6 key dietary antioxidants with defined dietary intake reference ranges that are considered important for brain health. Adult patients completed the 24-hour recall-face-to-face interview to calculate estimated nutrient intake. Nutrients were assessed individually and were also summarized into a summary score of intakes. Individual nutrients, summary nutrient intake, were compared with recommended dietary requirement (RDA) to assess the adequacy, body mass index was calculated, and medical records were abstracted for diagnoses of TBI. Results: A total of 71 TBI patients were complete the study, the majority were young age between 18-30 years, half of patients were classified as mild TBI while 12.7% and 40.8% were classified as moderate and severe TBI respectively based on Glasgow Coma Scale (GCS). Motor vehicle accidents were the most common cause of TBI followed by falls from height. One fourth of patients were underweight, while (47.9%) were normal weight and 24% were overweight and/or obese. Most of patients (72%) were current smokers; no patient met the RDAs for all six dietary antioxidants. Eighteen patients only (25%) fulfilled the requirements for 4 or more nutrients, while 53 patients fulfilled 6 or fewer requirements. The overall daily intake of dietary antioxidants was significantly lower than the RDA. Discussion: The importance of micronutrients is often neglected. Diets failing to meet RDAs for important brain nutrients were common in an outpatient TBI clinic, with the worst mean scores of intakes for those patients compared with the estimated average requirements. Multidimensional treatment plans, perhaps incorporating some of the described nutritional adjuvants, will thus merit more investigations from both the bench and the bedside to elucidate effective strategies to best treat TBI patients.
... Proposed mechanisms involve the modulation of inflammation during injury, and they are thought to have neuroregenerative properties [52]. Additionally, anti-oxidant vitamins including C, D, and E have often been considered given the low side effect profile and possible benefit [53,54]. Creatine and turmeric supplementation have also been investigated in their potential role in mTBI management [55,56]. ...
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Purpose of the Review Concussion evaluation and management has changed significantly. Understanding proper recognition, evaluation, and management allows for improved provision of care to patients. This paper will approach this topic from a sideline to training room management versus the traditional clinic evaluation Recent Findings Research is continuing to refine and examine tools to assist in proper concussion evaluation. Concussion recovery protocols are becoming more conservative as patients are taking longer to recover than previously thought. Treatment of concussion is becoming more sophisticated and patient involved. Summary Concussion research has increased dramatically over the last 30 years changing our approach to diagnosis and treatment. The area of concussion will continue to evolve as research continues to look at effective tools and markers for diagnosis and effective treatment protocols become substantiated through research.
... For example, the supraphysiological dosing of vitamins and nutrients (mainly flavonoids and omega-3 fatty acids) for treatment of brain injury is now well established with strong evidence backing their use. 28 However, high doses of chlorogenic acid are known to increase plasma homocysteine levels. 29 This kind of unexpected spinoff is more pronounced in the case of antioxidants, as they function as antioxidants at physiological dose, while occasionally at higher amounts a pro-oxidant activity is observed. ...
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Sayali Savant, Shraddha Srinivasan, Anil Kumar Kruthiventi Arna Immuno Ingredients Private Limited, Mumbai, Maharashtra, IndiaCorrespondence: Anil Kumar KruthiventiArna Immuno Ingredients Private Limited, 1st Floor, 41/44, Minoo Desai Marg, Colaba, Mumbai, 400005, IndiaTel +91 954 550 0481Fax +91 22 674 900 001Email anil.kumar@arnaimmuno.comAbstract: SARS-CoV-2 infection has caused, and is continuing to cause, considerable human suffering. Studies on the viral pathogenesis has resulted in convergent findings from several lines of evidence on the entry and spread of the virus in the host. These studies have also revealed a strong association between innocuous inflammation, ageing and metabolic disorders, with SARS-CoV-2 infection and its prognosis. Diet helps modulate inflammation, and nutraceuticals can inhibit viral entry. Hence, we have collated literature on antiviral nutraceuticals effective against other similar coronaviruses. The objective of this study is to comprehensively review available information on the antiviral activity of nutraceuticals and to discuss the implications of these findings in designing a diet that would boost the innate immunity and act as preventive care against COVID-19. This review highlights the fundamental impact of nutraceuticals and diet on inhibition of viral entry and provides a new perspective on the prevention and treatment of COVID-19.Keywords: SARS-CoV-2, diet, plant protease inhibitors, polyphenols, bioactive peptides
... 35 Several herbs and traditional medicines (e.g., ginseng, gingko biloba), flavonoids, and other nutrients (magnesium, zinc, carnitine, omega-3 fatty acids) as well as vitamins (e.g., B 2 , B 3 , B 6 , B 9 , C, D, E) have been reported to treat brain injury. 36 Wheeler et al. 37 demonstrated that healthy microglia are required for the protection against lethal CoV encephalitis in mice. ...
Article
The severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) breakout has caused millions of infections with thousands of deaths worldwide. Still, the number of infected cases with deaths is increasing day by day. Unfortunately, to date, we do not have a single specific remedy for it. Along with the protective measures, respiratory and/or circulatory supports and some non-specific anti-viral drug therapies have been reported to fight against this pandemic. So far, 165 vaccine candidates have been in various stages of clinical trials, of which 26 are in human trials. Besides Oxford University’s vaccine many others have already been able to garner worldwide response, it is still a long way to go. On the other hand, the discovery of vaccines is also delaying drug therapy approaches. In this case, we can focus on dietary supplements, especially vitamin-rich foods, as an alternative treatment. This writing focuses on the effects of dietary contents, especially the diets containing vitamins on the management of coronavirus disease 2019 (Covid-19).
... In recent years, vitamins, minerals and other essential nutrients show a great potential as primary therapies and attract much attention from researchers. This therapy, known as Nutraceutical therapy, can be an excellent choice for the treatment of patients with brain injuries (6,7). The process of atherosclerosis is characterized by arterial remodelling that causes the accumulation of progressive subendothelic plaques through a series of complex cellular processes that occur in the walls of the arteries with inflammation playing an important role in its various phases (8). ...
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Aim Accumulated evidence suggests that vitamin A and D agonists can alleviate the development of atherosclerosis. Therefore, the aim of this study was to determine the effect of vitamin A and D combination supplement on interleukin-1β (IL-1β) and clinical outcome in ischemic stroke. Methods A single-blind, randomized controlled trial was conducted on ischemic stroke patients at Adam Malik Hospital between March 2018 to February 2019. The patients were randomized into 4 groups of the treatment consisting of supplementation using vitamin A or D only, combination of vitamin A and D, and placebo group, all given for 12 weeks. Clinical outcome was determined using the National Institute of Health Stroke Scale (NIHSS). At the time of admission and after the treatment was completed, all patients were measured for vitamin A, vitamin D, and IL-1β serum level, and NIHSS score. Results From the total of 120 patients, in the combination group there were significant increments on both vitamin A (p=0.04) and vitamin D (p=0.01) serum level after 12 weeks of the treatment, compared to the other groups. In conjunction, IL-1β serum level showed a significant decrement in the combination group (p
... Vitamin D is involved in many cellular activities in the body including cell apoptosis, oxidative stress, inflammation, and excitotoxicity [4]. Vitamin D is metabolized in the liver into 25-hydroxyvitamin D (25(OH)D) [5]. ...
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PurposeReduced cognitive function associated with aging has gained increasing attention as the US population ages. Magnesium plays a critical role in vitamin D biosynthesis and metabolism; and deficiencies in magnesium and vitamin D show associations with poor cognition. However, no study has examined their interaction. This study aimed to evaluate the associations of magnesium intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, indicating vitamin D status, with cognition, and interaction between these nutrients in older adults.Methods Based on the National Health and Nutrition Survey (NHANES) 2011–2014, the study included 2466 participants aged ≥ 60 years who completed the Digit Symbol Substitution Test (DSST) and had data available on serum 25(OH)D and magnesium intake. Cognitive impairment was defined as a DSST score lower than the lowest quartile. Serum 25(OH)D concentrations were measured by HPLC-tandem mass spectrometry.ResultsHigher total magnesium intake was independently associated with higher DSST scores (highest quartile vs lowest: β = 4.34, 95% CI 1.14–7.54). The association of total magnesium intake with high DSST score was primarily observed among women, non-Hispanic whites, physically active participants and those with sufficient vitamin D status, although the interactions were not significant. The odds of cognitive impairment was reduced with increasing intake of total magnesium (p trend < 0.01) and higher level of serum 25(OH)D (p trend = 0.05).Conclusions Findings suggest that high magnesium intake alone may improve cognitive function in older adults, and the association may be stronger among subjects with sufficient vitamin D status. Further studies are needed to confirm these findings.
... Therefore, the quality of food consumed and/or supplementation of adjuvants and nutraceuticals is of fundamental importance in order to provide significant protection in the case of increased ROS and RNS formation [48,49]. Although the link between oxidative/nitrosative damage and TBI is evident and the awareness that deficiency in antioxidant-rich foods in the daily diet may further exacerbate TBI symptoms is highly plausible, there are still no clear evidence of successful antioxidant therapies in the clinical setting [50], despite a continuous growth of studies, reporting either preclinical or clinical data, using supplementation with natural or synthetic low molecular weight antioxidants, that have appeared in the literature in the last decades as potentially useful treatments in TBI [18,51]. This tendency is certainly due to different reasons, including the lack of standardized, clearly effective pharmacological approaches of TBI patients, the increased knowledge of the molecular mechanisms underlying cerebral damage after TBI, and the lack of unwanted side effects for the large majority of low molecular weight antioxidants. ...
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Due to multiplicity of causes originating a traumatic brain injury (TBI), TBI is a highly heterogeneous pathology, characterized by high mortality and disability rates. TBI is an acute neurodegenerative event, potentially and unpredictably evolving into sub-chronic and chronic neurodegenerative events, with transient or permanent neurologic, cognitive and motor deficits, for which no valid standardized therapies are available. A vast body of literature demonstrated that TBI-induced oxidative/nitrosative stress is involved in the development of both acute and chronic neurodegenerative disorders. Cellular defenses against this phenomenon are largely dependent on low molecular weight antioxidants, most of which are consumed with diet or as nutraceutical supplements. A large number of studies have evaluated the efficacy of antioxidant administration efficacy to decrease TBI-associated damage, in various animal TBI models and in a limited number of clinical trials. Points of weakness of preclinical studies are represented by the large variability in the TBI model adopted, in the antioxidant tested, in the timing, dosages and routes of administration used, and in the variety of molecular and/or neurocognitive parameters evaluated. The analysis of the very few clinical studies does not allow strong conclusions to be drawn on the real effectiveness of antioxidant administration to TBI patients. Standardizing TBI models and different experimental conditions, as well as testing the efficacy of administration of a cocktail of antioxidants rather than only one, should be mandatory. According to some promising clinical results, it appears that sports-related concussion is probably the best type of TBI to test benefits of antioxidant administration.
... It is generally accepted that highly unsaturated n-3 fatty acids (n-3 HUFA) or long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), particularly 20:5 n-3 (eicosapentaenoic acid [EPA]) and 22:6 n-3 (docosahexaenoic acid [DHA]) positively affect human health such as early development, and the prevention of some diseases (Vonder Haar et al., 2016). According to the FA profile of cod frame (Table 3), the most abundant FAs was determined as DHA (23.0-24.9 ...
Article
This study aimed at evaluating proximate composition, phosphorous content, amino acid (AA) and fatty acid (FA) profiles of cod (Gadus morhua) frame at five different sampling times (March 2017 to March 2018). Furthermore, the valorization possibility of cod frame by application of enzymatic hydrolysis was investigated using the samples from September 2017. In terms of protein content, this sample showed a significantly (P < 0.05) higher level (16.5%) compared to the other samples, whereas lipid and phosphorous contents varied in a narrow range of 0.9-1.1% and 2.9-4.4%, respectively, (P < 0.05). Furthermore, the total amino acids (AAs) content varied from about 98 to 155 mg/g in minced cod frame. Enzymatic hydrolysis of minced cod frame (MCF) and heated cod meat (HCM) was carried out by application of Alcalase and Neutrase, either individually or sequentially to obtain fish protein hydrolysate (FPH) and bone powder rich in phosphorus and calcium. The protein content of FPH varied from 76% to 84% and soluble-nitrogen in trichloroacetic acid (SN-TCA) index varied from 30.6-40.3%, resulting in similar trends for yield and nitrogen recovery. Considerable amounts of phosphorus and calcium (330 and 583 g/kg, respectively) were recovered from the cod frame bones after enzymatic hydrolysis. This study showed that it is possible to produce bone powder rich in phosphorous and calcium as well as peptides from the cod frame. Thus, the cod frame side-stream can be converted from its current use as mink feed ingredient into higher value products for human consumption, without generating new waste products.
... 23,24 Vitamins are nutrients or organic compounds that are essential for supporting the normal physiological functioning, growth, and health of the body. 25 One important reason that vitamins are needed is that they play an indirect role in catalysis, in which enzymes speed up chemical reactions. ...
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Ginseng is well known to treat various diseases. Ginsenoside Rg3 exhibits a variety of pharmacological activities including cardiovascular protective effects. Vitamins utilized as supplements have minimal interactions with other drugs making them attractive targets for therapeutics. Here, we prepared Rg3-enriched Korean ginseng catalyzed by vitamin (REKVG) and evaluated its ability to improve hypertension in spontaneously hypertensive rats (SHRs). The ginsenoside content in both Korean Red ginseng (KRG) and REKVG were analyzed using high-performance liquid chromatography (HPLC). Male SHRs and Wistar-Kyoto rats (WKYs) were randomly divided into 6 groups (WKY saline, WKY KRG, WKY REKVG, SHR saline, SHR KRG, and SHR REKVG). KRG and REKVG were orally administered once daily to the rats at a dose of 10 mg/kg for 6 weeks, and blood pressure was measured in live rats using the tail-cuff method. Human umbilical vein endothelial cells were used for the in vitro experiment. HPLC chromatograms revealed that the concentration of ginsenoside Rg3 in REKVG was much higher than that in KRG. The administration of REKVG significantly decreased the systolic blood pressure in SHRs at the end of 6 weeks as compared to KRG. Further, REKVG use resulted in a dose-dependent increase in Akt and endothelial nitric oxide synthase (eNOS) phosphorylation and NO production in endothelial cells. In addition, the administration of REKVG significantly increased Akt and eNOS phosphorylation and increased plasma NO levels in SHRs. We conclude that REKVG effectively lowers the blood pressure in rats and therefore could be considered for use in preventing or improving hypertension.
... It is important to note that exogenous ALC administration is also metabolized for energy via the TCA cycle in astrocytes and neurons within the forebrain [93]. In this sense, ALC incorporated into GABA, glutamate, and glutamine via TCA cycle metabolism protects against TBI-induced secondary damage [99]. In agreement to this view, previous studies have demonstrated the ability of this compound in activating antioxidant gene expressions [100] and general anti-inflammatory actions [101]. ...
Article
Traumatic brain injury (TBI) is a devastating condition that often triggers a sequel of neurological disorders that can last throughout lifespan. From a metabolic viewpoint, the compromising of the energy metabolism of the brain has produced evidence linking the severity of brain injury to the extent of disturbances in the cerebral metabolism. The cerebral metabolic crisis, however, displays that regional heterogeneity varies temporally post-injury. It is important to note that energy generation and mitochondrial function are closely related and interconnected with delayed secondary manifestations of brain injury, including early neuromotor dysfunction, cognitive impairment, and post-traumatic epilepsy (PTE). Given the extent of post-traumatic changes in neuronal function and the possibility of amplifying secondary cascades, different therapies designed to minimize damage and retain/restore cellular function after TBI are currently being studied. One of the possible strategies may be the inclusion of ergogenic compounds, which is a class of supplements that typically includes ingredients used by athletes to enhance their performance. The combination of these compounds offers specific physiological advantages, which include enhanced energy availability/metabolism and improved buffering capacity. However, the literature on their effects in certain biological systems and neurological diseases, such as TBI, has yet to be determined. Thus, the present review aims to discuss the role of ergogenic compounds popularly used in secondary damage induced by this neurological injury. In this narrative review, we also discuss how the results from animal studies can be applied to TBI clinical settings.
... A number of studies have shown that oral consumption of nutritional support or supplements may have significant benefit to the individual [43]. Several nutrients that have shown preliminary promise as aids in treating traumatic brain injury, in particular, choline, creatine, n-3 fatty acids, and zinc [44][45][46][47][48]. In addition, if full nutritional support (caloric intake) is initiated immediately following the injury, there is a significant reduction in the impact of infections and overall complications [49,50]. ...
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Currently, there are no approved therapeutic drugs for the treatment of traumatic brain injury (TBI), and new targets and approaches are needed to provide relief from the long-term effects of TBI. Recent studies suggest that nutrition plays a critical role in improving the outcome from TBI in both civilians and military personnel. We have previously shown that GrandFusion® (GF) diets improved recovery from cerebral ischemia and enhanced physical activity and endurance in rodent models. We, therefore, sought to determine the impact of a prophylactic diet enriched in fruits and vegetables on recovery from TBI in the controlled cortical impact rodent model. Results demonstrated that mice fed the diets had improved neuromotor function, reduced lesion volume, increased neuronal density in the hippocampus and reduced inflammation. As previously shown, TBI increases cathepsin B as part of the inflammasome complex resulting in elevated inflammatory markers like interleukin-1β (IL-1β). Consumption of the GF diets attenuated the increase in cathepsin B levels and prevented the increase in the proapoptotic factor Bax following TBI. These data suggest that prior consumption of diets enriched in fruits and vegetables either naturally or through powdered form can provide protection from the detrimental effects of TBI.
... This question was asked to determine personal practice regarding supplements and to introduce the concept of vitamins/minerals as CAM options. 12 Of all MHP's surveyed, 93.16% (109 of 117) incorrectly believe that the Food and Drug Administration (FDA) does not control herbal supplements the way they do prescription medications although 99.15% (116 of 117) correctly agreed that it could be dangerous to mix herbals and/or supplements with prescription medication. 4 Surprisingly, most respondents (89 of 117) disagreed with the statement that "vitamin and mineral supplements are generally risk-free". ...
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Neuropsychiatric and mental health symptoms affect an estimated 37% of the U.S. population and are often refractory to standard, conventional medical treatment. Adults with more than one neuropsychiatric symptom, such as depression, anxiety, insomnia, attention deficits, headaches, excessive sleepiness, and memory loss are disproportionally more likely to seek complementary and alternative medicine (CAM) options for their symptoms. Despite the growing popularity of CAM usage, (estimated at more than 30 percent of all adults by the National Centers on Complementary and Integrative Healthcare (NCCIH), there is very little known about mental health practitioner (MHP) attitudes, knowledge and understanding about CAM practices. A survey of 295 MHP's from multiple disciplines was conducted in order to investigate knowledge of, and attitudes towards, utilizing CAM treatments. Results suggest that many MHP's are unaware that they are using CAM approaches and are lacking knowledge regarding evidence for the use of CAM for mental health symptoms. © 2017 Center for Food and Biomolecules, National Taiwan University
... 121 The PL precursor combination tested here satisfies several requirements: 1) the relevance of the targeted mechanism (i.e., there is a reported sustained decrease of 25-35% in several PL classes post-injury after TBI; 2) the treatment tested can increase brain PL levels after 4-6 weeks of supplementation (as shown by Cansev and colleagues in aged rats 122 and our data here); and 3) the PL precursor preparation has been previously shown to restore brain connectivity and reduce hippocampal loss in patients, in early AD, as supported by clinical trials with FC. 34,123,124 TBI triggers many injury mechanisms, which should be addressed using multi-modal treatments. 125 Specialized nutrient interventions have the benefit of addressing multi-modal mechanisms, 126 and FC is a unique concept focused on the support of membrane integrity through provision of precursors required for PL formation. Injury in the nervous system triggers an extensive reorganization of circuits ipsilaterally and in the opposite hemisphere, and it could be hypothesized that FC might provide support for such restorative processes. ...
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Traumatic brain injury (TBI) leads to cellular loss, destabilisation of membranes, disruption of synapses and altered brain connectivity, and increased risk of neurodegenerative disease. A significant and long-lasting decrease in phospholipids (PL), essential membrane constituents, has recently been reported in plasma and brain tissue, in human and experimental TBI. We hypothesised that supporting PL synthesis post-injury could improve outcome after TBI. We tested this hypothesis using a multi-nutrient combination designed to support the biosynthesis of phospholipids and available for clinical use. The multi-nutrient Fortasyn® Connect (FC) contains polyunsaturated omega-3 fatty acids, choline, uridine, vitamins, co-factors required for PL biosynthesis, and has been shown to have significant beneficial effects in early Alzheimer's disease. Male C57BL/6 mice received a controlled cortical impact injury and then were fed a control diet or a diet enriched with FC for 70 days. FC led to a significantly improved sensorimotor outcome and cognition, reduced lesion size and oligodendrocyte loss, and it restored myelin. It reversed the loss of the synaptic protein synaptophysin and decreased levels of the axon growth inhibitor Nogo-A, thus creating a permissive environment. It decreased microglia activation and the rise in ß-amyloid precursor protein and restored the depressed neurogenesis. The effects of this medical multi-nutrient suggest that support of PL biosynthesis after TBI, a new treatment paradigm, has significant therapeutic potential in this neurological condition for which there is no satisfactory treatment. The multi-nutrient tested has been used in dementia patients, is safe and well-tolerated, which would enable rapid clinical exploration in TBI.
... Numerous pharmaceutical products studied as potential therapies for TBI have been unsuccessful in translation to clinical application, in part due to the multidimensional nature of damage from brain trauma (Gao et al., 2017). The most promising novel treatments for TBI have the potential to impact multiple aspects of the secondary injury cascade (Margulies, Hicks, & Combination Therapies for Traumatic Brain Injury Workshop, 2009;Vonder Haar, Peterson, Martens, & Hoane, 2016). ...
Article
Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mito-chondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI.
... In addition to DHA, there are many other nutritional interventions that may be viable therapies for TBI (Cook et al., 2008;Vonder Haar et al., 2016;Scrimgeour and Condlin, 2014). Focusing solely on fortifying the gut, there are many nutrients that may strengthen the integrity of the intestinal barrier. ...
Article
As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.
... Promising experimental treatment encompasses therapies using nutraceuticals (vitamins, herbs and flavonoids) and with nutrients. Several of these nutrients like carnitine, magnesium, omega-3 fatty acids and zinc, have shown promise for clinical applications particularly with regard to polydrug treatment [73]. Recent studies in rodent TBI models using exendin-4, Nacetyl-l-cysteine and salubrinal revealed positive treatment findings to treat brain injury on [74][75][76]. ...
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Background: Traumatic brain injury (TBI) is a result of an external physical force to the head that traumatically injures the brain. It is a major public health problem worldwide and mainly results from falls, vehicle accidents and violence. Clinical problem: The management of TBI, causing a wide spectrum of possible health outcomes, has barely changed over the years as encouraging outcomes from many pre-clinical therapeutic and pharmacological studies have only rarely been translated to the clinical situation. New management options: In the last decades management of TBI is rapidly advancing and new innovative imaging modalities with sophisticated treatment options by using nanomedicine based drug delivery systems are under investigation. Nano formulations such as PLGA, exosomes and liposomes have the advantage of a targeted and controlled delivery of their cargo, such as diagnostic probes and/or therapeutic drugs. Summary: Here we provide an overview of new promising pre-clinical developments in TBI management that may find their way to the clinic in the near future. Nanotechnology and nanomedicine in TBI intervention may establish new platforms for targeted drug delivery to the traumatized brain to improve the quality of life and survival of TBI patients.
... This is probably a result of the fact that niacin plays important roles in DNA synthesis and repairs, myelination and dendritic growth, cellular calcium signaling, and may act as a potent antioxidant in mitochondria in brain tissue. 51,52 Some better physical test results were associated with higher intakes of niacin and vitamin B6, which take part in carbohydrate, fat and protein metabolism, play a role in the synthesis of sex and stress-related hormones and enable the proper functioning of the nervous system. Additionally, dietary vitamin B6 status is probably a determinant of the concentration of carnosine, a dipeptide associated with skeletal muscle performance. ...
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Objectives The study is a case-control analysis of whether depression impairs physical and cognitive functioning and quality of life, and whether there is a relationship between nutrient deficiencies and these adverse changes. Patients and methods A total of 130 older subjects participated in the study: 65 with diagnosed depression (16 men and 49 women) and 65 age- and sex-matched controls without depression. All patients underwent comprehensive geriatric assessment. Nutritional state was assessed with the Mini Nutritional Assessment, cognitive performance was evaluated by the Mini-Mental State Examination and physical functioning by the Timed “Up & Go” test and handgrip strength. The pattern of consumption of various nutrients was analyzed in detail. Results The differences in cognitive functioning observed between the groups were related to specific nutrient intake, as was handgrip strength to some extent. The differences in nutritional status, several functional tests and muscle strength were related to both the presence of depression and inappropriate consumption of certain nutrients. Conclusion The incidence of falls and poor quality of life may be partially associated with the presence of depression. The inappropriate intake of selected nutrients may impair the functioning and quality of life of older adults with depression, such as the excess consumption of sucrose and insufficient consumption of protein, fiber, eicosapentaenoic acid, niacin and vitamin B6. Particular nutrients should be translated into dietary patterns which allow the individual patient to address these nutrient deficiencies.
... A new field using complementary and alternative medical therapeutic approaches appears to be very promising following TBI [18]. An increasing number of natural compounds, with multifaceted pharmacological effects, may provide essential neuroprotection and increased cellular health following TBI to promote greater recovery [6,10,23,36,50,[52][53][54]. ...
Article
We have previously shown that pycnogenol (PYC) increases antioxidants, decreases oxidative stress, suppresses neuroinflammation and enhances synaptic plasticity following traumatic brain injury (TBI). Here, we investigate the effects of PYC on cognitive function following a controlled cortical impact (CCI). Adult Sprague-Dawley rats received a CCI injury followed by an intraperitoneal injection of PYC (50 or 100 mg/kg). Seven days post trauma, subjects were evaluated in a Morris water maze (MWM) and evaluated for changes in lesion volume. Some animals were evaluated at 48 h for hippocampal Fluoro-jade B (FJB) staining. The highest dose of PYC therapy significantly reduced lesion volume, with no improvement in MWM compared to vehicle controls. PYC failed to reduce the total number of FJB positive neurons in the hippocampus. These results suggest that the reduction of oxidative stress and neuroinflammation are not the key components of the secondary injury that contribute to cognitive deficits following TBI.
... Magnesium is another mineral that has been shown to improve recovery following TBI in pre-clinical models. 70 Furthermore, Wahls and colleagues found that magnesium was one of the four key nutrients that correlated with improved somatic scores when supplemented following mild TBI in humans. 71 Magnesium is commonly depleted following TBI likely through interaction with transient receptor potential melastatin, which leads to neuronal cell death. ...
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Studies using traditional treatment strategies for mild traumatic brain injury (TBI) have produced limited clinical success. Interest in treatment for mild TBI is at an all time high due to its association with the development of chronic traumatic encephalopathy and other neurodegenerative diseases, yet therapeutic options remain limited. Traditional pharmaceutical interventions have failed to transition to the clinic for the treatment of mild TBI. As such, many pre-clinical studies are now implementing non-pharmaceutical therapies for TBI. These studies have demonstrated promise, particularly those that modulate secondary injury cascades activated after injury. Because no TBI therapy has been discovered for mild injury, researchers now look to pharmaceutical supplementation in an attempt to foster success in human clinical trials. Non-traditional therapies, such as acupuncture and even music therapy are being considered to combat the neuropsychiatric symptoms of TBI. In this review, we highlight alternative approaches that have been studied in clinical and pre-clinical studies of TBI, and other related forms of neural injury. The purpose of this review is to stimulate further investigation into novel and innovative approaches that can be used to treat the mechanisms and symptoms of mild TBI.
... , neutraceuticals (Hoane et al., 2003(Hoane et al., , 2005(Hoane et al., , 2008Gómez-Pinilla, 2008;Guseva et al., 2008;Kokiko-Cochran et al., 2008;Peterson et al., 2012;Agrawal et al., 2015;Vonder Haar et al., 2015), rehabilitative approaches Maegele et al., 2005;Matter et al., 2011;Cheng et al., 2012;Monaco et al., 2013Monaco et al., , 2014Bondi et al., , 2015aGriesbach et al., 2012Griesbach et al., , 2015Kreber and Griesbach, 2016), and stem cell transplantation (Gao et al., 2006;Riess et al., 2007;Valle-Prieto and Conget, 2010;Zanier et al., 2011;De La Peña et al., 2015;Patel and Sun, 2016) have been shown to confer motor and/or cognitive benefits in research laboratories using clinically relevant experimental models (Kline andDixon, 2001, Cernak, 2005;Morales et al., 2005;Morganti-Kossmann et al., 2010;Marklund and Hillered, 2011;Johnson et al., 2015), but few have successfully translated to the clinic (Doppenberg et al., 2004;Beauchamp et al., 2008;Menon, 2009). The lack of translational success has prompted researchers and clinicians to reconsider the likelihood that single or monotherapeutic approaches may not be the best, or even the appropriate, course of action for optimal recovery after TBI and that combining drug treatments that target multiple and complementary mechanisms of action should be evaluated. ...
Article
Traumatic brain injury (TBI) is a significant health care crisis that affects two million individuals in the United Sates alone and over ten million worldwide each year. While numerous monotherapies have been evaluated and shown to be beneficial at the bench, similar results have not translated to the clinic. One reason for the lack of successful translation may be due to the fact that TBI is a heterogeneous disease that affects multiple mechanisms, thus requiring a therapeutic approach that can act on complementary, rather than single, targets. Hence, the use of combination therapies (i.e., polytherapy) has emerged as a viable approach. Stringent criteria, such as verification of each individual treatment plus the combination, a focus on behavioral outcome, and post-injury vs. pre-injury treatments, were employed to determine which studies were appropriate for review. The selection process resulted in 37 papers that fit the specifications. The review, which is the first to comprehensively assess the effects of combination therapies on behavioral outcomes after TBI, encompasses five broad categories (inflammation, oxidative stress, neurotransmitter dysregulation, neurotrophins, and stem cells, with and without rehabilitative therapies). Overall, the findings suggest that combination therapies can be more beneficial than monotherapies as indicated by 46% of the studies exhibiting an additive or synergistic positive effect versus on 19% reporting a negative interaction. These encouraging findings serve as an impetus for continued combination studies after TBI and ultimately for the development of successful clinically relevant therapies.
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When mild traumatic brain injury (mTBI) occurs following an impact on the head or body, the brain is disrupted leading to a series of metabolic events that may alter the brain’s ability to function and repair itself. These changes may place increased nutritional demands on the body. Little is known on whether nutritional interventions are safe for patients to implement post mTBI and whether they may improve recovery outcomes. To address this knowledge gap, we conducted a systematic review to determine what nutritional interventions have been prescribed to humans diagnosed with mTBI during its acute period (<14 days) to support, facilitate, and result in measured recovery outcomes. Methods: Databases CINAHL, PubMed, SPORTDiscus,Web of Science, and the Cochrane Library were searched from inception until January 6, 2021; 4,848 studies were identified. After removing duplicates and applying the inclusion and exclusion criteria, this systematic review included 11 full papers. Results: Patients that consumed enough food to meet calorie and macronutrient (protein) needs specific to their injury severity and sex within 96 h post mTBI had a reduced length of stay in hospital. In addition, patients receiving nutrients and non-nutrient support within 24–96 h post mTBI had positive recovery outcomes. These interventions included omega-3 fatty acids (DHA and EPA), vitamin D, mineral magnesium oxide, amino acid derivative N-acetyl cysteine, hyperosmolar sodium lactate, and nootropic cerebrolysin demonstrated positive recovery outcomes, such as symptom resolution, improved cognitive function, and replenished nutrient deficiencies (vitamin D) for patients post mTBI. Conclusion: Our findings suggest that nutrition plays a positive role during acute mTBI recovery. Following mTBI, patient needs are unique, and this review presents the potential for certain nutritional therapies to support the brain in recovery, specifically omega-3 fatty acids. However, due to the heterogenicity nature of the studies available at present, it is not possible to make definitive recommendations. Systematic review registration: The systematic review conducted following the PRISMA guidelines protocol was registered (CRD42021226819), on Prospero. KEYWORDS: brain injury - traumatic, mild traumatic brain injury (mTBI), concussion, omega 3 (n-3) polyunsaturated fatty acids, vitamin, supplementation, nutrition
Chapter
Sport-related concussion (SRC) is an ever-growing public health concern in the athletic and medical realms as parents, healthcare professionals, and athletes hope to learn more about the risks and safety precautions around specific sports and injuries. Various organizations have helped refine the definition of an SRC along with numerous other factors of athlete care including appropriate sideline evaluation, recognition of symptoms, and how to safely return to learn (RTL) and return to play (RTP). This chapter will provide details with the latest evidence-based research of relevant SRC biomechanics, pathophysiology, epidemiology, clinical presentation, expected recovery timelines, pertinent risk factors, available preventative and treatment strategies, potential roles of various diagnostic testing available, and a case report of an athlete presenting with an SRC. This chapter aims to educate all healthcare professionals who provide different levels of care for elite athletes (EAs) along their road to recovery.KeywordsConcussionAthleteSportMental healthTraumatic brain injuryHead and neck
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Concussion, sometimes called a mild traumatic brain injury (mTBI), is an acquired brain injury resulting in alterations to brain function underpinned by a sequence of neuropathological and neurometabolic events that can result in excitotoxicity, oxidative stress, oedema, neuroinflammation and cell death. To date, pharmaceutical therapies have had limited success in treating TBI, presenting considerable interest in nutritional therapies in the form of dietary supplementation to alleviate the deleterious pathological sequelae following neurotrauma. Many nutritional supplements have low toxicity, few drug interactions, and are already approved for human use making them attractive potential therapies following a concussion. In the setting of brain injury models, a considerable body of preclinical evidence has accumulated supporting the use of nutritional supplements including essential fatty acids, vitamins, minerals, amino acids, polyphenols, bioflavonoids and other bioactive compounds to facilitate aspects of functional recovery. Here, we review studies presenting diet supplements as therapeutic strategies as potential treatments for mTBI or to augment neurological resistance against mTBI in experimental models, as well as emerging therapeutic targets including the gut microbiome, and psychedelic and non-psychedelic compounds derived from fungi.
Chapter
Traumatic brain injury (TBI) has become a leading health problem with no effective treatment. TBI imposes a significant burden of morbidity and mortality and is a major challenge in the intensive care unit (ICU). The lack of proven effective treatments for TBI is related to the range of severity of injury, the complexity of approaching a disease that involves multiple tissue and cell types, rapid onset of pathophysiology, common co-morbidity presentation, and other environmental and developmental factors. However, prompt treatment for TBI is critical, including surgery, intensive care, drugs, and alternative treatments, since cerebral edema can result in a variety of pathologies associated with primary and secondary injuries, as well as death. There is a need for interventions to be performed with the aim of preventing or treating the complications and accelerating the recovery of patients with TBI. Considering that nutritional support, when combined with other TBI treatments, is very effective, in this narrative review we focused on the role of herbal and nutrient supplements, identifying their protective effects on TBI outcomes. Combination of vitamins, amino acids, plant extracts, and herbs as a nutritional support may reduce recovery time in people with TBI, which work synergistically to repair TBI damage and improve areas of brain and body function that are most affected by TBI. Effective nutritional support is an emerging factor that may be added to help improving outcomes of TBI, but further clinical trials and empirical studies are definitely needed in this rapidly progressing field.
Article
Oxidative stress plays a crucial role in traumatic brain injury (TBI) pathogenesis. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) formed in excess after TBI synergistically contribute to secondary brain damage together with lipid peroxidation products (reactive aldehydes) and inflammatory mediators. Furthermore, oxidative stress, endoplasmic reticulum stress and inflammation potentiate each other. Following TBI, excessive oxidative stress overloads the endogenous cellular antioxidant system leading to cell death. To combat oxidative stress, several antioxidant therapies were tested in preclinical animal models of TBI. These include free radical scavengers, activators of antioxidant systems, Inhibitors of free radical generating enzymes and antioxidant enzymes. Many of these therapies showed promising outcomes including reduced edema, blood-brain barrier (BBB) protection, smaller contusion volume, and less inflammation. In addition, many antioxidant therapies also promoted better sensory, motor, and cognitive functional recovery after TBI. Overall, preventing oxidative stress is a viable therapeutic option to minimize the secondary damage and to improve the quality of life after TBI.
Chapter
Biorefineries are the physical embodiment of bioeconomy. The idea of the circular economy is based on four crucial pillars (i) products are designed so that consumables are returned to the biosphere without harm after a sequence of uses, (ii) durables are designed to maximize their valuable reuse or up-grade, (iii) renewable energy is used to fuel the process, (iv) waste, generated where the costs of if its reuse and recycling are higher than the value created, potentially ceases to exist because products undergo a cycle of disassembly and reuse. This Chapter deals with the cascading concept applied to food waste-based feedstocks at different scale-up levels, with a focus on the valuable bio-based outputs, to endorse a sequential, circular, and sustainable use of food waste biomass.
Article
Omega-3 fatty acids are known to reduce platelet aggregation and decrease risk of cardiovascular or cerebrovascular disease. Currently, there are no published systematic reviews that address the effect of omega-3 supplementation after a cerebral injury. This review addresses the benefit of omega-3 supplementation after intracranial injury, including traumatic brain injury and intracranial hemorrhage. Five studies met all of the inclusion criteria and were included in the review. Two trials reported improved clinical outcomes, measured as incidence of postoperative bleeding and symptomatic or cerebral vasospasm, while 3 saw no impact from omega-3 supplementation. In conclusion, omega-3 fatty acid supplementation may be beneficial in patients who have experienced intracranial injury.
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Aquiring the recommended daily allowance of vitamins is crucial for maintaining homeo�static balance in humans and other animals. A deficiency in or dysregulation of vitamins adversely affects the neuronal metabolism, which may lead to neurodegenerative diseases. In this article, we discuss how novel vitamin-based approaches aid in attenuating abnormal neuronal functioning in neurodegeneration-based brain diseases such as Alzheimer’s disease, Parkinson’s disease, Hunt�ington’s disease, Amyotrophic lateral sclerosis, and Prion disease. Vitamins show their therapeutic activity in Parkinson’s disease by antioxidative and anti-inflammatory activity. In addition, different water- and lipid-soluble vitamins have also prevented amyloid beta and tau pathology. On the other hand, some results also show no correlation between vitamin action and the prevention of neurodegenerative diseases. Some vitamins also exhibit toxic activity too. This review discusses both the beneficial and null effects of vitamin supplementation for neurological disorders. The de�tailed mechanism of action of both water- and lipid-soluble vitamins is addressed in the manuscript. Hormesis is also an essential factor that is very helpful to determine the effective dose of vitamins. PubMed, Google Scholar, Web of Science, and Scopus were employed to conduct the literature search of original articles, review articles, and meta-analyses.
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Vitamin D deficiency (Ddef) alters morphology and outcomes after a stroke. We investigated the interaction of Ddef following post-stroke systemic inflammation and evaluated whether administration of progesterone (P) or vitamin D (D) will improve outcomes. Ddef rats underwent stroke with lipopolysaccharide (LPS)-induced systemic inflammation. Rats were randomly divided into 9 groups and treated with P, D, or vehicle for 4 days. At day 4, rats were tested on different behavioral parameters. Markers of neuronal inflammation, endoplasmic reticulum stress, oxidative stress, white matter integrity, and apoptosis were measured along with immune cell populations from the spleen, thymus, and blood. Severely altered outcomes were observed in the Ddef group compared to the D-sufficient (Dsuf) group. Stroke caused peripheral immune dysfunction in the Dsuf group which was worse in the Ddef group. Systemic inflammation exacerbated injury outcomes in the Dsuf group and these were worse in the Ddef group. Monotherapy with P/D showed beneficial functional effects but the combined treatment showed better outcomes than either alone. Ddef as a comorbid condition with stroke worsens stroke outcomes and can delay functional recovery. Combination treatment with P and D might be promising for future stroke therapeutics in Ddef.
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Complementary and integrative healthcare (CIH) is becoming part of musculoskeletal and rehabilitation medicine. In the past, providers or patients would use complementary modalities after conventional Western medicine failed, whereas now individuals are incorporating these approaches into treatment plans from the start. As such, it is important for providers to have an understanding of CIH, so as to provide the patient with a good understanding of how these approaches will be incorporated into their care plan. If providers fail to glean an understanding of these practices, then they may limit their patients with treatment strategies or may be unable to build strong rapport with patients who focus on these modalities.
Article
Omega-3-enriched fish oil (FO) and caloric restriction (CR) are nutritional therapeutic approaches that exert an important impact on brain function, behavior, memory, and neuroprotection. Here, we investigate the synergic effects of both therapeutic approaches combined (CR + FO) on behavior (memory, anxiety-like behavior, antidepressant-like behavior), as well as its association with hippocampal brain-derived neurotrophic factor (BDNF) concentrations. Adult male Wistar rats were divided into four dietary groups: Control group (C) - chow ad libitum; CR group - 30% CR, considering C group food intake; FO group - FO-enriched chow ad libitum; and CR + FO group - FO-enriched 30% CR chow. After 12 weeks of dietary treatment, behavioural analysis set was conducted, and hippocampal BDNF concentrations were measured. FO group presented anxiolytic-like and antidepressant-like behaviors as well as improved memory in the Morris’ water maze. These effects were attenuated by the combined CR + FO treatment. FO group also presented higher BDNF concentrations. There was a positive association between the number of entries in the platform quadrant in the MWM and hippocampal BDNF concentrations (β = 0.39; R² = 0.15; p = 0.042) and an inverse association between forced swim immobility time and BDNF concentrations (β = -0.39; R² = 0.15; p = 0.041). Taken together, our data showed that the 12-week FO dietary treatment promoted anxiolytic-like and antidepressant-like behaviors as well as memory improvement, and these effects were associated with BDNF concentrations. Synergic effects of interventions attenuated FO-related behavioral responses and BDNF concentrations and probably reduced hippocampal neuroplasticity.
Chapter
The growing awareness of the key role of nutrition to human health status has greatly contributed to the spread of a new feeding concept: the functional nutrition. Nowadays, the foods are not exclusively a source of energy for the performance of normal metabolic processes of the body, but also the unique source of bioactive compounds. These compounds contribute to “maximize” the human health status and to “minimize” the risk of occurrence of diseases. The main challenge facing researchers and food industries is to ensure the quality attributes of foods and, simultaneously, to improve the food functionality. The present book chapter give an overview of the scientific studies conducted at the Food Science area of D3A (Department of Agricultural, Food and Environmental Sciences) with the aim to enhance the quality and the functionality of foods.
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Nutritional adequacy is frequently compromised after brain injury, consequent to initial pathology as well as iatrogenic factors. This also compromises fluid handling, pharmacodynamics, and subsequent wound healing. Early feeding improves outcomes, with the jejunal route offering greater success but more complexity in placement. Motility disorders are common but significantly compromise physiology, while stress gastric erosion remains a significant risk. Refeeding syndrome is a risk in cases of malnutrition. Hyperglycemia has adverse effects, but interventions and the precise thresholds for these remain uncertain. Immune-enhancing formulas can reduce infection rates. Combination therapies of vitamins and trace elements offer possibilities for improvement.
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It is increasingly recognized that tissue-specific nutrient deficiencies can exist in the absence of whole-body deficiency and that these deficiencies may result from disease or disease-related physiological processes. Brain and central nervous system tissues require adequate nutrient levels to function. Many nutrients are concentrated in the cerebrospinal fluid relative to the serum in healthy individuals, and other nutrients resist depletion in the presence of whole-body nutrient depletion. The endothelial, epithelial, and arachnoid brain barriers work in concert to selectively transport, concentrate, and maintain levels of the specific nutrients required by the brain while also blocking the passage of blood-borne toxins and pathogens to brain and central nervous system tissues. These barriers preserve nutrient levels within the brain and actively concentrate nutrients within the cerebrospinal fluid and brain. The roles of physical and energetic barriers, including the blood–brain and blood–nerve barriers, in maintaining brain nutrient levels in health and disease are discussed. Expected final online publication date for the Annual Review of Nutrition Volume 39 is August 21, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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According to the 2017 Global Nutrition Report, 88% percent of the world’s countries are seriously burdened by at least two forms of malnutrition (Hawkes & Fanzo, 2017). This report includes alarming estimations that more than 2 billion people are lacking essential micronutrients including iodine, vitamin A, and iron, and 2 billion more are overweight or obese. Moreover, the authors note that 155 million children are considered stunted (low height for age), 55 million are considered wasted (low weight for height), while 41 million are considered overweight. The concurrent problems of undernutrition along with overweight and obesity are described by the World Health Organization (WHO, 2017) as the double burden of malnutrition.
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The majority of brain injuries that lead to cerebral palsy, developmental disability, and mental health disorders have their onset in utero. These lifelong conditions come with great economic and emotional burden as they impact function in nearly all domains of affected individuals' lives. Unfortunately, current therapeutic options are limited. There remains a focus on rescue, rehabilitation, and regeneration after the injury has occurred, rather than aiming to prevent the initial injury. Prevention would imply treating the mother during pregnancy to alter the fetal environment and in turn, treat the fetus. Fear of harming the developing fetus remains as a result of errors of the past such as the release of thalidomide. In this review, we outline evidence from animal studies and clinical trials that have explored maternal dietary supplementation with natural health products (including nutraceuticals and functional foods) for perinatal brain injury prevention. Namely, we discuss magnesium sulphate, creatine, choline, melatonin, resveratrol and broccoli sprouts/sulforaphane. Although clinical trials have only been completed in this realm for magnesium sulphate, results in animal models have been promising, suggesting that this is a productive avenue for further research. Natural health products may provide safe, effective, affordable, and easily accessible prevention of fetal brain injury and resulting lifelong disabilities.
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Complementary and alternative medicine (CAM) is a group of diverse medical and health care systems, practices, and products that are not presently considered to be a part of conventional medicine. Integrative medicine combines treatment with conventional medical practices and elements of CAM in which there is strong evidence in efficacy and safety. Although there is growing interest in the integrative medical approach in treating the patient population with traumatic brain injury, there is a paucity in high-quality clinical trials supporting its use. This article reviews the background and current clinical data concerning some of the more common CAM interventions.
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Previously, we were able to demonstrate the neuroprotective effect of quercetin in an animal model of acute traumatic spinal cord injury. The objective of the present study was to determine whether any neuroprotective effect is seen when quercetin is administered in an animal model of traumatic brain injury. Twenty-six adult male Sprague-Dawley rats were submitted to moderate fluid percussion injury in the anterior midline position. Animals were divided into two experimental groups: one group received 25 mumol/kg quercetin starting 1 h after injury, while animals in the second group received saline vehicle (n = 13 per group). Eight animals were used as uninjured healthy controls. Eight animals in each experimental group were sacrificed at 24 h, while five animals per group were allowed to recover for 72 h following injury. Compound action potential amplitudes (CAPAs) were recorded on 400-microm vibrotome sections of the corpus callosum superfused with oxygenated artificial CSF (n = 3 per animal) in 20 experimental animals and five healthy controls. Three brains from animals in each experimental group and healthy controls were used for histological, immunocytochemical and biochemical analysis after sacrifice at 24 h. CAPAs in uninjured animals had a mean of 1.12 mV. This decreased to 0.55 mV in saline vehicle-treated injured animals by 24 h and changed little over the next 3 days. CAPAs were significantly better at 0.82 mV at 24 h and 0.76 mV at 3 days in quercetin-treated injured animals when compared to injured saline vehicle controls. Quercetin significantly prevented decrease of glutathione levels and decreased myeloperoxidase activity. We conclude that this dietary flavonoid has therapeutic potential following brain trauma.
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Ginkgo biloba is a natural medicine used for cognitive impairment and Alzheimer's disease. We conducted this review to evaluate the effectiveness and safety of Ginkgo biloba for mild cognitive impairment and Alzheimer's disease. We searched for randomized clinical trials of Ginkgo biloba for mild cognitive impairment and Alzheimer's disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to 1st December, 2014. We conducted meta-analyses using RevMan 5.2 software. 21 trials involving 2608 patients were included. The general methodological quality of included trials was moderate to poor. Compared with conventional medicine alone, Ginkgo biboba in combination with conventional medicine was superior in improving cognitive function as measured by Mini-Mental State Examination (MMSE) at 24 weeks for Alzheimer's disease (MD 2.39, 95% CI 1.28 to 3.50, P<0.0001) and mild cognitive impairment (MD 1.90, 95% CI 1.41 to 2.39, P<0.00001), and activities of daily living as measured by Activity of Daily Living (ADL) at 24 weeks for Alzheimer's disease (MD -3.72, 95% CI -5.68 to -1.76, P=0.0002). When compared with placebo or conventional in individual trials, Ginkgo biboba demonstrated similar but inconsistent findings. Adverse events were mild. Ginkgo biloba appears to be beneficial in improving cognitive function, activities of daily living, and global clinical assessment in patients with mild cognitive impairment or Alzheimer's disease. However, due to limited sample size, inconsistent findings and methodological quality of included trials, the findings should be interpreted with caution.
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The potentially life-threatening effects of total body ionizing radiation exposure have been known for more than a century. Despite considerable advances in our understanding of the effects of radiation over the past six decades, efforts to identify effective radiation countermeasures for use in case of a radiological/nuclear emergency have been largely unsuccessful. Vitamin E is known to have antioxidant properties capable of scavenging free radicals, which have critical roles in radiation injuries. Tocopherols and tocotrienols, vitamin E analogs together known as tocols, have shown promise as radioprotectors. Although the pivotal mechanisms of action of tocols have long been thought to be their antioxidant properties and free radical scavenging activities, other alternative mechanisms have been proposed to drive their activity as radioprotectors. Here we provide a brief overview of the effects of ionizing radiation, the mechanistic mediators of radiation-induced damage, and the need for radiation countermeasures. We further outline the role for, efficacy of, and mechanisms of action of tocols as radioprotectors, and we compare and contrast their efficacy and mode of action with that of another well-studied chemical radioprotector, amifostine.
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Patients enrolled in clinical trials for traumatic brain injury (TBI) may present with heterogeneous features over a range of injury severity, such as diffuse axonal injury, ischemia, edema, hemorrhage, oxidative damage, mitochondrial and metabolic dysfunction, excitotoxicity, inflammation, and other pathophysiological processes. To determine whether combination therapies might be more effective than monotherapy at attenuating moderate TBI or promoting recovery, the National Institutes of Health funded six preclinical studies in adult and immature male rats to evaluate promising acute treatments alone and in combination. Each of the studies had a solid rationale for its approach based on previous research, but only one reported significant improvements in long-term outcomes across a battery of behavioral tests. Four studies had equivocal results because of a lack of sensitivity of the outcome assessments. One study demonstrated worse results with the combination in comparison with monotherapies. While specific research findings are reported elsewhere, this article provides an overview of the study designs, insights, and recommendations for future research aimed at therapy development for TBI.
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Inflammation is an important component of the response to traumatic brain injury (TBI). Progesterone has been shown to inhibit neuroinflammation following (TBI) and may do so through Toll-like receptor (TLR)-mediated pathways. In vitro studies indicate that 1,25-dihydroxyvitamin D(3) (VDH) may also modulate the inflammatory response through the TLR4 pathway. This study tested the hypothesis that PROG and VDH would exert additive and synergistic neuroprotective effects compared with individual treatment by modulating TLR4/NF-κB-mediated inflammation pathways after TBI in rats. Bilateral medial frontal cortical impact injury was induced in young adult Sprague-Dawley rats. Progesterone (i.p., 16 mg kg(-1) body weight) and VDH (1 µg kg(-1) body weight) were injected separately or combined at 1 and 6 hours after surgery. Rats were killed 24 hours post-surgery and peri-contusional brain tissue harvested for immunostaining and protein measurement. TLR4, phosphorylation of NF-κB, neuronal loss and astrocyte activation were significantly reduced with combination treatment after TBI compared to each agent given individually. At 24 hours after TBI, combination therapy shows greater efficacy in reducing neuroinflammation compared to progesterone and VDH given separately, and does so by modulating the TLR4/NF-κB signalling pathway.
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In contrast to considerable data demonstrating a decrease in cytochrome P450 (CYP) activity in inflammation and infection, clinically, traumatic brain injury (TBI) results in an increase in CYP and UDP glucuronosyltransferase (UGT) activity. The objective of this study was to determine the effects of TBI alone and with treatment with erythropoietin (EPO) or anakinra on the gene expression of hepatic inflammatory proteins, drug-metabolizing enzymes, and transporters in a cortical contusion impact (CCI) injury model. Microarray-based transcriptional profiling was used to determine the effect on gene expression at 24 h, 72 h, and 7 days post-CCI. Plasma cytokine and liver protein concentrations of CYP2D4, CYP3A1, EPHX1, and UGT2B7 were determined. There was no effect of TBI, TBI + EPO, or TBI + anakinra on gene expression of the inflammatory factors shown to be associated with decreased expression of hepatic metabolic enzymes in models of infection and inflammation. IL-6 plasma concentrations were increased in TBI animals and decreased with EPO and anakinra treatment. There was no significant effect of TBI and/or anakinra on gene expression of enzymes or transporters known to be involved in drug disposition. TBI + EPO treatment decreased the gene expression of Cyp2d4 at 72 h with a corresponding decrease in CYP2D4 protein at 72 h and 7 days. CYP3A1 protein was decreased at 24 h. In conclusion, EPO treatment may result in a significant decrease in the metabolism of Cyp-metabolized drugs. In contrast to clinical TBI, there was not a significant effect of experimental TBI on CYP or UGT metabolic enzymes.
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One of the largest challenges in experimental neurotrauma work is the development of models relevant to the human condition. This includes both creating similar pathophysiology as well as the generation of relevant behavioral deficits. Recent studies have shown that there is a large potential for the use of discrimination tasks in rats to detect injury-induced deficits. The literature on discrimination and TBI is still limited, however. The current study investigated motivational and motor factors that could potentially contribute to deficits in discrimination. In addition, the efficacy of a neuroprotective agent, nicotinamide, was assessed. Rats were trained on a discrimination task and motivation task, given a bilateral frontal controlled cortical impact TBI (+ 3.0 AP, 0.0 ML from bregma), and then reassessed. They were also assessed on motor ability and Morris water maze (MWM) performance. Experiment 1 showed that TBI resulted in large deficits in discrimination and motivation. No deficits were observed on gross motor measures; however, the vehicle group showed impairments in fine motor control. Both injured groups were impaired on the reference memory MWM, but only nicotinamide-treated rats were impaired on the working memory MWM. Nicotinamide administration improved performance on discrimination and motivation measures. Experiment 2 evaluated retraining on the discrimination task and suggested that motivation may be a large factor underlying discrimination deficits. Retrained rats improved considerably on the discrimination task. The tasks evaluated in this study demonstrate robust deficits and may improve the detection of pharmaceutical effects by being very sensitive to pervasive cognitive deficits that occur after frontal TBI.
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Background: Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. We investigated the efficacy and safety of progesterone in a large, prospective, phase 3 randomized clinical trial. Methods: We conducted a multinational placebo-controlled trial, in which 1195 patients, 16 to 70 years of age, with severe TBI (Glasgow Coma Scale score, ≤8 [on a scale of 3 to 15, with lower scores indicating a reduced level of consciousness] and at least one reactive pupil) were randomly assigned to receive progesterone or placebo. Dosing began within 8 hours after injury and continued for 120 hours. The primary efficacy end point was the Glasgow Outcome Scale score at 6 months after the injury. Results: Proportional-odds analysis with covariate adjustment showed no treatment effect of progesterone as compared with placebo (odds ratio, 0.96; confidence interval, 0.77 to 1.18). The proportion of patients with a favorable outcome on the Glasgow Outcome Scale (good recovery or moderate disability) was 50.4% with progesterone, as compared with 50.5% with placebo. Mortality was similar in the two groups. No relevant safety differences were noted between progesterone and placebo. Conclusions: Primary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials. (Funded by BHR Pharma; SYNAPSE ClinicalTrials.gov number, NCT01143064.).
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Neuroprotection, recovery of function, and gene expression were evaluated in an animal model of traumatic brain injury (TBI) after a combination treatment of nicotinamide (NAM) and progesterone (Prog). Animals received a cortical contusion injury over the sensorimotor cortex and were treated with either Vehicle, NAM, Prog or a NAM/Prog combination for 72 h and compared to a craniotomy only (Sham) group. Animals were assessed in a battery of behavioral (fine and gross motor and sensory) tasks or a histological assessment at 24 h post-injury assessing lesion cavity size, degenerating neurons, and reactive astrocytes. Microarray-based transcriptional profiling was used to determine treatment specific changes on gene expression. Our results confirm the beneficial effects of treatment with either NAM or Prog demonstrating significant improvements in recovery of function, and a reduction in lesion cavitation, degenerating neurons, and reactive astrocytes 24 h post-injury. The combination treatment of NAM and Prog led to a significant improvement in both neuroprotection at 24 h post-injury and recovery of function in sensorimotor related tasks when compared to individual treatments. The NAM/Prog-treated group was the only treatment group to show a significant reduction of cortical loss 24 h post-injury. The combination appears to affect inflammatory and immune processes, reducing expression of a significant number of genes in both pathways. Further preclinical trials using NAM and Prog as a combination treatment should be done to identify the window of opportunity, to determine the optimal duration of treatment and to evaluate the combination in other pre-clinical models of TBI.
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Child health is a growing concern at the global level, as infectious diseases and preventable conditions claim hundreds of lives of children under the age of five in low-income countries. Approximately 7.6 million children under five years of age died in 2011, calculating to about 19 000 children each day and almost 800 every hour. About 80 percent of the world's under-five deaths in 2011 occurred in only 25 countries, and about half in only five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan and China. The implications and burden of such statistics are huge and will have dire consequences if they are not corrected promptly. This paper reviews essential interventions for improving child health, which if implemented properly and according to guidelines have been found to improve child health outcomes, as well as reduce morbidity and mortality rates. It also includes caregivers and delivery strategies for each intervention. Interventions that have been associated with a decrease in mortality and disease rates include exclusive breastfeeding, complementary feeding strategies, routine immunizations and vaccinations for children, preventative zinc supplementation in children, and vitamin A supplementation in vitamin A deficient populations.
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Objective: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. Methods: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population–based Cardiovascular Health Study between 1992–1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992–1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. Results: During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23–4.13) and 1.53 (95% CI: 1.06–2.21) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02–4.83) and 1.69 (95% CI: 1.06–2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L. Conclusion: Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.
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Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. In the present study, we performed a widely-used model of TBI to determine the neuroprotective propriety of palmitoylethanolamide (PEA) and the antioxidant effect of a flavonoid luteolin (Lut), given as a co-ultramicronized compound Co-ultraPEALut. We demonstrated that the treatment with Co-ultraPEALut resulted in a significant improvement of motor and cognitive recovery after controlled cortical impact (CCI), as well as markedly reducing lesion volumes. Moreover, our results revealed the ability of Co-ultraPEALut, to reduce brain trauma through modulation of NF-κB activation. In addition, treatment with Co-ultraPEALut significantly enhanced the post-TBI expression of the neuroprotective neurotrophins GDNF compared to vehicle. Co-ultraPEALut at the dose of 1 mg/kg, also modulated apoptosis, the release of cytokine and ROS, the activation of chymase, tryptase and nitrotyrosine and inhibited autophagy. Thus, our data demonstrated that Co-ultraPEALut at a lower dose compared to PEA alone, can exert neuroprotective effects and the combination of both could improve their ability to counteract the neurodegeneration and neuroinflammation induced by TBI.
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Proper nutrition is critical for recovery from traumatic brain injury (TBI). Prompt enteral feeding of moderate to severe TBI patients has been associated with significantly lower mortality and rates of infection. Probiotic supplementation has been associated with significantly lower rates of infection in TBI and other trauma patients. Human studies have suggested that supplementation with omega 3 fats, vitamin D, NAcetylcysteine, branched chain amino acids, and zinc may be helpful for recovery from TBI. Animal TBI models have suggested that alphalipoic acid, magnesium, taurine, coenzyme Q10, and many phytonutrients (such as resveratrol) are also helpful. Unfortunately, recent human clinical trials with citicoline in TBI and stroke patients have produced disappointing results. Much more research is needed on multifaceted nutritional strategies to treat TBI patients in both the immediate postinjury phase and throughout the patients lifespan.
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Aim: Traumatic brain injury (TBI) leads to important and deleterious inflammation, as evidenced by edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. After TBI, the activation of cerebral vascular endothelial cells plays a crucial role in the pathogenesis of inflammation. In this study, we hypothesized that the activation of cerebral vascular endothelial cells plays a crucial role in the pathogenesis of inflammation and outcome after TBI. It may represent a key cellular target for statin therapy. Methods: In our study, cortical contusions were induced, and the effect of continuous treatment of simvastatin on behavior and inflammation in adult rats following experimental TBI was evaluated. The treatment group received 15 mg/kg of simvastatin daily for 3 days. Neurological function was assessed with the grip test. Results: The results showed that the non-treatment control group had a significantly greater increase in ICAM-1 expression from pre-injury to the post-injury 72 h time point as compared to the expression in treatment group. The treatment group had better neurological function as evidenced in a grip test performed from baseline to 72 h. The analysis of a western blot test and pathology also demonstrated reduced ICAM-1 expression and a smaller area of damage and tissue loss. Conclusion: Our findings suggest that simvastatin could attenuate the activation of cerebral vascular endothelial inflammatory response and decrease the loss of neurological function and brain tissue.
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Traumatic brain injury (TBI) is an acquired brain trauma that occurs when any sudden trauma/injury causes damage to the brain. TBI is characterized by tissue damage and imbalance in the cerebral blood fl ow and metabolism. It has been established through laboratory experiments that the dietary supplementation of omega-3 fatty acids (FAs) could reduce the oxidative stress developed in brain due to TBI. The inclusion of omega-3 FA in diet could normalize the levels of brain-derived neurotrophic factor (BDNF), and thus, it could restore the survival and plasticity of neuronal cells. BDNF improves the synaptic transmission by regulating synapsin 1 and cyclic adenosine monophosphate (cAMP) response element binding protein. The brain tissue analysis of TBI models supplemented with omega-3 polyunsaturated fatty acids (PUFAs) showed signifi cantly reduced lipid peroxidation, nucleic acid and protein oxidation, thereby promoting neuronal and glial cell survival. Thus, omega-3 FA intake could be considered as a therapeutic option to reduce the secondary neuronal damages initiated by TBI.
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Traumatic brain injury (TBI) is a significant public health concern. On average, 1.7 million people sustain a TBI annually and about 5.3 million Americans are living with a TBI-related disability. As the leading cause of death and disability in persons under 45 years old, there is a need for developing evidence-based interventions to reduce morbidity from this injury. So far, despite encouraging preclinical results, almost all neuroprotection trials have failed to show any significant efficacy in the treatment of clinical TBI. The cascade of molecular and cellular changes following TBI involves plasticity in many different neurochemical systems, which represent putative targets for neurotherapeutic interventions. Accordingly, a successful TBI treatment may have to simultaneously attenuate many injury factors. The purpose of this review is to highlight four promising nutritional intervention options that have been identified, omega-3, zinc, vitamin D and glutamine, and to provide an up-to-date summary regarding their apparent efficacy for affecting TBI.
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Previous studies did not draw a consistent conclusion about the effects of marine-derived n-3 polyunsaturated fatty acids (PUFAs) on fasting blood level of C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). A comprehensive search of Web of Science, PubMed, Embase and Medline (from 1950 to 2013) and bibliographies of relevant articles was undertaken. Sixty-eight RCTs with a total of 4601 subjects were included in the meta-analysis. Marine-derived n-3 PUFAs supplementation showed a lowering effect on Marine-derived n-3 PUFAs supplementation had a significant lowering effect on TNF-α, IL-6 and CRP in three groups of subjects (subjects with chronic non-autoimmune disease, subjects with chronic autoimmune disease and healthy subjects). A significant negative linear relationship between duration and effect size of marine-derived n-3 PUFAs supplementation on fasting blood levels of TNF-α and IL-6 in subjects with chronic non-autoimmune disease was observed, indicating that longer duration of supplementation could lead to a greater lowering effect. A similar linear relationship was also observed for IL-6 levels in healthy subjects. Restricted cubic spline analysis and subgroup analysis showed that the lowering effect of marine-derived n-3 PUFAs on CRP, IL-6 and TNF-α in subjects with chronic non-autoimmune disease became weakened when body mass index was greater than 30 kg/m(2). The effect of marine-derived n-3 PUFAs from dietary intake was only assessed in subjects with chronic non-autoimmune disease, and a significant lowering effect was observed on IL-6, but not on CRP and TNF-α. Marine-derived n-3 PUFAs supplementation had a significant lowering effect on CRP, IL-6 and TNF-α level. The lowering effect was most effective in non-obese subjects and consecutive long-term supplementation was recommended.
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Abstract Traumatic brain injury (TBI) causes neuronal cell death as well as microglial activation and related neurotoxicity that contribute to subsequent neurological dysfunction. Poly (ADP-ribose) polymerase (PARP-1) induces neuronal cell death through activation of caspase-independent mechanisms, including release of apoptosis inducing factor (AIF), and microglial activation. Administration of PJ34, a selective PARP-1 inhibitor, reduced cell death of primary cortical neurons exposed to N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG), a potent inducer of AIF-dependent cell death. PJ34 also attenuated lipopolysaccharide and interferon-γ-induced activation of BV2 or primary microglia, limiting NF-κB activity and iNOS expression as well as decreasing generation of reactive oxygen species and TNFα. Systemic administration of PJ34 starting as late as 24 h after controlled cortical impact resulted in improved motor function recovery in mice with TBI. Stereological analysis demonstrated that PJ34 treatment reduced the lesion volume, attenuated neuronal cell loss in the cortex and thalamus, and reduced microglial activation in the TBI cortex. PJ34 treatment did not improve cognitive performance in a Morris water maze test or reduce neuronal cell loss in the hippocampus. Overall, our data indicate that PJ34 has a significant, albeit selective, neuroprotective effect after experimental TBI, and its therapeutic effect may be from multipotential actions on neuronal cell death and neuroinflammatory pathways.
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Omega-3 fatty acids are crucial for proper development and function of the brain where docosahexaenoic acid (DHA), the primary omega-3 fatty acid in the brain, is retained avidly by the neuronal membranes. We investigated the effect of DHA depletion in the brain on the outcome of traumatic brain injury (TBI). Pregnant mice were put on an omega-3 fatty acid adequate or deficient diet from gestation day 14 and the pups were raised on the respective diets. Continuation of this dietary regime for three generations resulted in approximately 70% loss of DHA in the brain. Controlled cortical impact was delivered to both groups of mice to produce severe TBI and the functional recovery was compared. Compared to the omega-3 adequate mice, the DHA depleted mice exhibited significantly slower recovery from motor deficits evaluated by the rotarod and the beam walk tests. Furthermore, the DHA deficient mice showed greater anxiety-like behavior tested in the open field test as well as cognitive deficits evaluated by the novel object recognition test. The level of alpha spectrin II breakdown products, the markers of TBI, was significantly elevated in the deficient mouse cortices, indicating that the injury is greater in the deficient brains. This observation was further supported by the reduction of NeuN positive cells around the site of injury in the deficient mice, indicating exacerbated neuronal death after injury. These results suggest an important influence of the brain DHA status on TBI outcome.
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Traumatic brain injury (TBI) occurs in response to an acute insult to the head and is recognized as a major risk factor for Alzheimer's disease (AD). Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (Aβ) deposits, tauopathy, and neuroinflammation. Additional studies involving animal models of AD indicate that some AD-related genotypic determinants may be critical factors enhancing temporal and phenotypic symptoms of TBI. Thus in the present study, we examined sub-acute effects of moderate TBI delivered by a gas-driven shock tube device in Aβ depositing Tg2576 mice. Three days later, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3) activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolished these accelerated pathologies. This study lays the groundwork for a safe and natural compound that could prevent or treat TBI with minimal or no deleterious side effects in combat personnel and others at risk or who have experienced TBI.
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Traumatic brain injury (TBI) is accompanied by substantial accumulation of biomarkers of oxidative stress and depletion of antioxidants reserve which initiate chain reactions that damage brain cells. The present study investigated the role of ascorbic acid and α-tocopherol on the severity and management of TBI in rats. Wistar rats were subjected to closed head injury using an accelerated impact device. Rats were administered 45 mg/kg and 60 mg/kg body weight of ascorbic acid, α-tocopherol or a combination of the two vitamins for 2 weeks pre- and post injury. Blood and brain tissue homogenates were analyzed for vitamin C, vitamin E, malondialdehyde, superoxide dismutase, and creatine kinase activities. The results indicated that TBI caused significant (P < 0.05) decreased in vitamins C and E levels in the blood and brain tissue of TBI-untreated rats. The activities of superoxide dismutase in TBI rats were markedly reduced when compared with non traumatized control and showed a tendency to increased following supplementation with vitamins C and E. Supplementation of the vitamins significantly (P < 0.05) reduced malondialdehyde in the treatment groups compared with the TBI-untreated group. The study indicated that pre and post treatment with ascorbic acid and α-tocopherol reduced oxidative stress induced by brain injury and effectively reduced mortality rate in rats.
Article
Magnesium reduces edema following traumatic brain injury (TBI), although the associated mechanisms are unknown. Recent studies suggest that edema formation after TBI may be related to alterations in aquaporin-4 (AQP4) channels. In this study, we characterize the effects of magnesium administration on AQP4 immunoreactivity following TBI. Male Sprague-Dawley rats were injured by impact-acceleration diffuse TBI and a subgroup was administered 30 mg/kg magnesium sulphate 30 minutes after injury. Animals were fixed by perfusion 5 hours later, which corresponded to the time of maximum edema formation according to previous studies. One half of the brain was cut using a Vibratome and the other half blocked in paraffin wax. Wax and Vibratome sections were immunostained for detection of AQP4 by light and electron microscopy, respectively. In untreated animals, AQP4 immunoreactivity was increased in the subependymal inner glia limitans and the subpial outer glia limitans, and decreased in perivascular astrocytic processes in the cerebrum and brain stem. In contrast, animals treated with magnesium sulphate had AQP4 profiles similar to normal and sham control animals. We conclude that magnesium decreases brain edema formation after TBI, possibly by restoring the polarized state of astrocytes and by down-regulation of AQP4 channels in astrocytes.
Article
Riboflavin is unique among the water-soluble vitamins in that milk and dairy products make the greatest contribution to its intake in Western diets. Meat and fish are also good sources of riboflavin, and certain fruit and vegetables, especially dark-green vegetables, contain reasonably high concentrations. Biochemical signs of depletion arise within only a few days of dietary deprivation. Poor riboflavin status in Western countries seems to be of most concern for the elderly and adolescents, despite the diversity of riboflavin-rich foods available. However, discrepancies between dietary intake data and biochemical data suggest either that requirements are higher than hitherto thought or that biochemical thresholds for deficiency are inappropriate. This article reviews current evidence that diets low in riboflavin present specific health risks. There is reasonably good evidence that poor riboflavin status interferes with iron handling and contributes to the etiology of anemia when iron intakes are low. Various mechanisms for this have been proposed, including effects on the gastrointestinal tract that might compromise the handling of other nutrients. Riboflavin deficiency has been implicated as a risk factor for cancer, although this has not been satisfactorily established in humans. Current interest is focused on the role that riboflavin plays in determining circulating concentrations of homocysteine, a risk factor for cardiovascular disease. Other mechanisms have been proposed for a protective role of riboflavin in ischemia reperfusion injury; this requires further study. Riboflavin deficiency may exert some of its effects by reducing the metabolism of other B vitamins, notably folate and vitamin B-6.
Article
Parkinson's disease(PD) is characterized by abnormalities in postural control and balance along with psychological issues like fear/anxiety, both affecting the fall rates.Thus,understanding whether balance issues remains same with increased fear of fall or vice a versa is essential for planning our treatment goals for PD patients. This study aimed at assessing correlation between balance performance and fear of falls in Parkinson's patients. 30 subjects of Parkinson disease were included in the study. Balance performance was assessedusing following outcome measures: Unified Parkinson Disease rating scale (UPDRSIIIsubscale items 27, 28, 29, 30), Berg Balance Scale (BBS), Timed Up and GO (TUG), Multidirectional Reach Test (MDRT) and fear of falls using Activity Specific Balance Confidence Scale (ABC) and Modified Fall Efficacy Scale (MFES).Out of the balance measures TUG shows significant moderate correlation with both ABC and MFES (p=0.01). UPDRS III shows poor but significant correlation only with MFE (p=0.04). MDRT BR shows moderate significant correlation with MFES (p=0.02). The other outcome measures showed no significant correlation. Thus, improvement in balance performance does not mean that the fear of fall or confidence level will also improve and should be considered as a different construct.
Article
Autors determine the clinical effectiveness of including cytoflavin in intensive care of patients with severe combined traumatic brain injury. A prospective blind randomized controlled study was conducted on two groups involving 101 participants. In group I (58 patients), the intensive care was standard. In group II (43 patients), the intensive care included cytoflavin which was added beginning with the second day of the post-traumatic period. For this purpose, 10 ml of cytoflavin was dissolved in 200 ml of 10% aqueous solution of glucose and was administered intravenously at a speed of 140 drops (7 ml) per minute within 7 days. The use of cytoflavin in complex intensive care of severe combined traumatic brain injury within two days after injury (with the proper correction of blood circulation and respiration) reduced the number of multiple organ dysfunctions, the number is purulent-septic complications, the time of regress in multiple organ dysfunctions, and the reanimation period in intensive care department on the average by a factor of 1.4 - 1.6 (p < 0.005).
Article
To determine the association of enteral nutrition (EN) with patient preinjury and injury characteristics and outcomes for patients receiving inpatient rehabilitation after traumatic brain injury (TBI). Prospective observational study. Nine rehabilitation centers. Patients (N=1701) admitted for first full inpatient rehabilitation after TBI. Not applicable. FIM at rehabilitation discharge, length of stay, weight loss, and various infections. There were many significant differences in preinjury and injury characteristics between patients who received EN and patients who did not. After matching patients with a propensity score of >40% for the likely use of EN, patients receiving EN with either a standard or a high-protein formula (>20% of calories coming from protein) for >25% of their rehabilitation stay had higher FIM motor and cognitive scores at rehabilitation discharge and less weight loss than did patients with similar characteristics not receiving EN. For patients receiving inpatient rehabilitation after TBI and matched on a propensity score of >40% for the likely use of EN, clinicians should strongly consider, when possible, EN for ≥25% of the rehabilitation stay and especially with a formula that contains at least 20% protein rather than a standard formula. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Article
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Certain patients appear to benefit when they receive immune enhancing additives, such as glutamine, arginine, and omega-3 fatty acids. We hypothesized that TBI patients given enteral feedings containing these supplements may have improved nutrition measures and infection rates when compared to standard tube feedings. This is a retrospective review of patients from a Level-One trauma center from July 2009 to July 2013. A total of 240 TBI patients received either an immune enhancing nutrition (IEN) formula (n = 126), or a standard formula (SF) (n = 114) based on the attending surgeon's preference. Data collected included demographic information, infection information and outcome measures. Patients were similar in terms of age, ISS, head AIS, and initial prealbumin level. Patients receiving IEN were found to have lower rates of blood stream infections (10.3% vs 19.3%, p < 0.05), whereas pneumonia and UTI rates were similar between groups. In addition, both groups had similar rates of all-cause mortality and hospital length of stay, however IEN patients spent longer in the ICU and on ventilators. In TBI patients receiving IEN, prealbumin levels were higher at the second, third, and fourth week of admission (week 2 - 22.2 vs 17.4, p = 0.006; week 3 - 24.6 vs 20.1, p = 0.04; week 4 - 26.3 vs 22.1, p = 0.19; week 5 - 25.8 vs 20.3, p = 0.21). This study suggests that patients with traumatic brain injury who receive IEN are more likely to have increased prealbumin levels perhaps reflecting improved nutrition throughout their hospital stay and may show some benefit in rates of infections, particularly in bacteremia. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.
Article
Oxidative stress may contribute to many pathophysiologic changes that occur after traumatic brain injury. In the current study, contemporary methods of detecting oxidative stress were used in a rodent model of traumatic brain injury. The level of the stable product derived from peroxidation of arachidonyl residues in phospholipids, 8-epi-prostaglandin F2α, was increased at 6 and 24 h after traumatic brain injury. Furthermore, relative amounts of fluorescent end products of lipid peroxidation in brain extracts were increased at 6 and 24 h after trauma compared with sham-operated controls. The total antioxidant reserves of brain homogenates and water-soluble antioxidant reserves as well as tissue concentrations of ascorbate, GSH, and protein sulfhydryls were reduced after traumatic brain injury. A selective inhibitor of cyclooxygenase-2, SC 58125, prevented depletion of ascorbate and thiols, the two major water-soluble antioxidants in traumatized brain. Electron paramagnetic resonance (EPR) spectroscopy of rat cortex homogenates failed to detect any radical adducts with a spin trap, 5,5-dimethyl-1-pyrroline N-oxide, but did detect ascorbate radical signals. The ascorbate radical EPR signals increased in brain homogenates derived from traumatized brain samples compared with sham-operated controls. These results along with detailed model experiments in vitro indicate that ascorbate is a major antioxidant in brain and that the EPR assay of ascorbate radicals may be used to monitor production of free radicals in brain tissue after traumatic brain injury.
Article
Previous studies in rodents have shown that after a moderate traumatic brain injury (TBI) with a controlled cortical impact (CCI) device, the adult-born immature granular neurons in the dentate gyrus are the most vulnerable cell type in the hippocampus. There is no effective approach for preventing immature neuron death after TBI. We found that tyrosine-related kinase B (TrkB), a receptor of brain-derived neurotrophic factor (BDNF), is highly expressed in adult-born immature neurons. We determined that the small molecule imitating BDNF, 7, 8-dihydroxyflavone (DHF), increased phosphorylation of TrkB in immature neurons both in vitro and in vivo. Pretreatment with DHF protected immature neurons from excitotoxicity-mediated death in vitro, and systemic administration of DHF before moderate CCI injury reduced the death of adult-born immature neurons in the hippocampus 24 hours after injury. By contrast, inhibiting BDNF signaling using the TrkB antagonist ANA12 attenuated the neuroprotective effects of DHF. These data indicate that DHF may be a promising chemical compound that promotes immature neuron survival after TBI through activation of the BDNF signaling pathway.
Article
Traumatic brain injury (TBI) is followed by a state of metabolic dysfunction, affecting the ability of neurons to use energy and support brain plasticity; there is no effective therapy to counteract the TBI pathology. Brain-derived neurotrophic factor (BDNF) has an exceptional capacity to support metabolism and plasticity, which highly contrasts with its poor pharmacological profile. We evaluated the action of a flavonoid derivative 7,8-dihydroxyflavone (7,8-DHF), a BDNF receptor (TrkB) agonist with the pharmacological profile congruent for potential human therapies. Treatment with 7,8-DHF (5mg/kg, ip, daily for 7days) was effective to ameliorate the effects of TBI on plasticity markers (CREB phosphorylation, GAP-43 and syntaxin-3 levels) and memory function in Barnes maze test. Treatment with 7,8-DHF restored the decrease in protein and phenotypic expression of TrkB phosphorylation after TBI. In turn, intrahippocampal injections of K252a, a TrkB antagonist, counteracted the 7,8-DHF induced TrkB signaling activation and memory improvement in TBI, suggesting the pivotal role of TrkB signaling in cognitive performance after brain injury. A potential action of 7,8-DHF on cell energy homeostasis was corroborated by the normalization in levels of PGC-1α, TFAM, COII, AMPK and SIRT1 in animals subjected to TBI. Results suggest a potential mechanism by which 7,8-DHF counteracts TBI pathology via activation of the TrkB receptor and engaging the interplay between cell energy management and synaptic plasticity. Since metabolic dysfunction is an important risk factor for the development of neurological and psychiatric disorders, these results set a precedent for the therapeutic use of 7,8-DHF in a larger context. Copyright © 2015. Published by Elsevier B.V.
Article
Magnesium sulfate is neuroprotective in preclinical models of stroke and has shown signals of potential efficacy with an acceptable safety profile when delivered early after stroke onset in humans. Delayed initiation of neuroprotective agents has hindered earlier phase 3 trials of neuroprotec