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Pathological varicosities: (A) immunofluorescent images of axonal swellings produced during dynamic stretch injury of cultured neurons, stained for tubulin (a), tau (b), amyloid precursor protein (c), and neurofilament (d); 246 (B) immunohistochemical stain against amyloid precursor protein, showing axonal varicosities in the corpus callosum of traumatic brain injury cases, caused by motor vehicle collision (a, e, f), falls (b, c), and blunt force trauma (d); 246 (C) confocal laser microscopy images of putamen tissue from Parkinson's disease cases, showing varicosities, stained for tyrosine hydroxylase (TH), α-synuclein (s-129), with a merged image; 292 (D) electron micrograph of TH immune reactivity showing an axonal (synaptic) varicosity in rat DRG as a result of sensory and sympathetic interactions; 284 (E) immunostained image of varicosity formation in a neuronal cell culture after exposure to prion protein peptide 106–126, showing varicosities (arrows 1–5); 239 (F) immunohistochemical stains showing varicosities and spheroids in a mouse model of Alzheimer's disease, stained for neurofilament (a, b, c) and the spinal cord of an early onset Alzheimer's disease case, stained for amyloid precursor protein (d). 289
Source publication
Postoperative cognitive dysfunction (POCD) is a decline in memory following anaesthesia and surgery in elderly patients. While often reversible, it consumes medical resources, compromises patient well-being, and possibly accelerates progression into Alzheimer's disease. Anesthetics have been implicated in POCD, as has neuroinflammation, as indicate...
Citations
... These seminal discoveries have been largely confirmed in subsequent studies showing the capability of pulsed PBM to afford complex cytoskeleton remodeling and changes in cell elastic modulus, leading to increased stem cell proliferation and improved wound healing (36), as well as to changes in cell migration and morphology (37,38). PBM-mediated cytoskeletal assembly and disassembly have also been implicated in neuroprotective responses (39). Moving further on this path will likely represent the avenue for an unprecedented understanding of some fundamental characteristics of our biology, hopefully disclosing new paradigms of cures for acute and chronic diseases. ...
Signaling molecules exhibit mechanical oscillations, entailing precise vibrational directionalities. These steering signatures have profound functional implications and are intimately connected with the onset of molecular electric oscillations and biophoton emission. We discuss biophotonic activity as a form of endogenous photobiomodulation, orchestrating the mechano-sensing/-transduction in signaling players. We focus on exogenous photobiomodulation in the form of pulsed wave modulation of selected light wavelengths to direct endogenous biophotonic activity and molecular cellular dynamics. We highlight the relevance of this strategy to target and reprogram the developmental potential of tissue-resident stem cells in damaged tissues, affording precision regenerative medicine without the need for cell or tissue transplantation.
... Therefore, prevention of POCD has become a major challenge for an increasing number of elderly patients. Studies have shown that there is a direct relationship between the incidence of POCD and nerve injury caused by an inflammatory response in the body [4]. However, there is no specific treatment for POCD currently. ...
Background
To observe the effects of conventional theatre nursing combined with transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive dysfunction (POCD) in elderly total knee arthroplasty (TKA) patients.
Methods
Forty elderly TKA patients were randomly divided into a conventional nursing (control) group and a TEAS group. Using conventional nursing, TEAS was used to stimulate the “Zusanli” and “Sanyinjiao” in the healthy leg of patients in the TEAS group. All patients received mini-mental (MMSE) scores 1 day before surgery (T0) and 1, 3, and 7 days after surgery (T1, T3, T7). Plasma levels of interleukin-1 (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and S100β were measured using venous blood samples.
Results
There were no significant differences in baseline clinical characteristics between the two groups. Compared to T0, the MMSE scores of patients in the control group were significantly reduced at T1 and T3 (P < 0.05). Compared to the control group, the MMSE scores of patients in the TEAS group increased significantly at T3 (P < 0.05). The incidence of POCD in the TEAS group was 10%, lower than in the control group (40%) (P < 0.05). The levels of IL-1β, IL-6, TNF-α and S-100β in patients in the TEAS group were lower than in the control group on days T1, T3 and T7 (P < 0.05).
Conclusion
Conventional intraoperative nursing combined with TEAS can reduce the incidence of POCD. The possible mechanism is related to the reduction of inflammatory response and neuronal injury with TEAS.
Clinical registration number: ChiCTR2300070281.
... Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in elderly patients following anesthesia and surgery (1,2). POCD is often characterized by memory loss and reduced cognitive dysfunction (3,4). ...
Neuroinflammation plays a key role in the pathogenesis of postoperative cognitive dysfunction (POCD). Results of our previous study demonstrated that dexmedetomidine (Dex) attenuates neuroinflammation in BV2 cells treated with lipopolysaccharide (LPS) by targeting the microRNA (miR)-340/NF-κB axis. However, the molecular mechanisms by which Dex improves POCD remain unclear. In the present study, the association between long non-coding (lnc)RNA small nucleolar RNA host gene 14 (SNHG14) and miR-340 in BV2 microglial cells was determined using a dual-luciferase reporter assay. In addition, SNHG14, miR-340 and NF-κB expression levels were measured in LPS-treated BV-2 cells and hippocampal tissues of mice with POCD, and an enzyme-linked immunosorbent assay was used to determine the levels of proinflammatory mediators. Results of the present study demonstrated that SNHG14 exhibited potential as a target of miR-340. In addition, SNHG14 knockdown increased the levels of miR-340 and reduced the levels of NF-κB in LPS-treated BV2 cells. In addition, Dex treatment significantly reduced the levels of SNHG14 and NF-κB, and elevated the levels of miR-340 in the hippocampus of aged mice with POCD. Moreover, Dex treatment notably decreased the expression levels of TNF-α, IL-1β, IL-2, IL-6, IL-8 and IL-12 in the hippocampus of aged mice with POCD by upregulating miR-340. The spatial memory impairments in aged mice with POCD were also notably increased following Dex treatment via upregulation of miR-340. Collectively, results of the present study demonstrated that Dex may protect microglia from LPS-induced neuroinflammation in vitro and attenuate hippocampal neuroinflammation in aged mice with POCD in vivo via the SNHG14/miR-340/NF-κB axis. The present study may provide further insights into the mechanisms underlying Dex in the treatment of POCD.
... Although the function of dendritic varicosities is still not fully understood, it is known that amacrine dendritic varicosities electrically isolate local input-output neuronal circuits [110]. Axonal varicosities, which are involved in the antidromic propagation of action potentials to the soma in a retrograde manner [111], likely play a role in neuron mechanosensation [112] and protection [113] in the CNS, and contribute to blood flow regulation in the peripheral nervous system [114]. The observed varicosities suggest the activation of neurons. ...
Introduction:
While most animals of the Muridae family are nocturnal, the gerbil displays diurnal activity and provides a useful model for visual system research. The purpose of this study was to investigate the localization of calcium-binding proteins (CBPs) in the visual cortex of the Mongolian gerbil (Meriones unguiculatus). We also compared the labeling of CBPs to those of gamma-aminobutyric acid (GABA)- and nitric oxide synthase (NOS)-containing neurons.
Material and methods:
The study was conducted on twelve adult Mongolian gerbils (3-4 months old). We used horseradish peroxidase immunocytochemistry and two-color fluorescence immunocytochemistry with conventional and confocal microscopy to assess CBPs localization in the visual cortex.
Results:
The highest density of calbindin-D28K (CB)- (34.18%) and parvalbumin (PV)-IR (37.51%) neurons was found in layer V, while the highest density of calretinin (CR)-IR (33.85%) neurons was found in layer II. The CB- (46.99%), CR- (44.88%), and PV-IR (50.17%) neurons mainly displayed a multipolar round/oval morphology. Two-color immunofluorescence revealed that only 16.67%, 14.16%, and 39.91% of the CB-, CR-, and PV-IR neurons, respectively, contained GABA. In addition, none of the CB-, CR-, and PV-IR neurons contained NOS.
Conclusions:
Our findings indicate that CB-, CR-, and PV-containing neurons in the Mongolian gerbil visual cortex are distributed abundantly and distinctively in specific layers and in a small population of GABAergic neurons but are limited to subpopulations that do not express NOS. These data provide a basis for the potential roles of CBP-containing neurons in the gerbil visual cortex.
... The application of additional irradiation from an external source, such as through the delivery of PBMt, may be hypothesized to modulate the EM properties of these ion channels to elicit a biological response that has a direct influence on neurotransmission. Indeed, Chow et al. and others have shown that the application of low-level laser irradiation on neurons in-vitro, induced axonal varicosities in the same way as pharmacological anesthetics, resulting in the blockade of neurotransmission and therefore conferring an analgesic effect [32,86,87]. Interestingly, a recent study has suggested that neuronal spheroids may be involved in the pathology of Alzheimer's disease [88]. ...
... It is also known that PBMt can directly target and modulate light-sensitive ion channels and signaling proteins to directly regulate microtubule function. Notable examples include firstly the weakly inward rectifying K channel (TWIK)-related spinal cord potassium channels (TRESK), which are important in photophobia, including in migraine with aura, [86] and secondly the chromophore neuropsin. Both have important roles in neuroplasticity and memory and also regulate microtubule-associated protein 2 (MAP2) [117]. ...
Despite a significant focus on the photochemical and photoelectrical mechanisms underlying photobiomodulation (PBM), its complex functions are yet to be fully elucidated. To date, there has been limited attention to the photophysical aspects of PBM. One effect of photobiomodulation relates to the non-visual phototransduction pathway, which involves mechanotransduction and modulation to cytoskeletal structures, biophotonic signaling, and micro-oscillatory cellular interactions. Herein, we propose a number of mechanisms of PBM that do not depend on cytochrome c oxidase. These include the photophysical aspects of PBM and the interactions with biophotons and mechanotransductive processes. These hypotheses are contingent on the effect of light on ion channels and the cytoskeleton, the production of biophotons, and the properties of light and biological molecules. Specifically, the processes we review are supported by the resonant recognition model (RRM). This previous research demonstrated that protein micro-oscillations act as a signature of their function that can be activated by resonant wavelengths of light. We extend this work by exploring the local oscillatory interactions of proteins and light because they may affect global body circuits and could explain the observed effect of PBM on neuro-cortical electroencephalogram (EEG) oscillations. In particular, since dysrhythmic gamma oscillations are associated with neurodegenerative diseases and pain syndromes, including migraine with aura and fibromyalgia, we suggest that transcranial PBM should target diseases where patients are affected by impaired neural oscillations and aberrant brain wave patterns. This review also highlights examples of disorders potentially treatable with precise wavelengths of light by mimicking protein activity in other tissues, such as the liver, with, for example, Crigler-Najjar syndrome and conditions involving the dysregulation of the cytoskeleton. PBM as a novel therapeutic modality may thus behave as “precision medicine” for the treatment of various neurological diseases and other morbidities. The perspectives presented herein offer a new understanding of the photophysical effects of PBM, which is important when considering the relevance of PBM therapy (PBMt) in clinical applications, including the treatment of diseases and the optimization of health outcomes and performance.
... The incidence of PND after non-cardiac major surgery was 7% to 26% and even higher than patients over 60-years-old, while the incidence of PND in patients undergoing cardia surgery may reach 30% to 80% within a few weeks after surgery and 10% to 60% in 3 to 6 months after surgery. [5] PND is associated with postoperative complications and worsened prognosis including chronic and neuropathic pain, increased hospitalization time/cost, and delayed recovery, [6,7] resulting in poor quality of life, increased financial burden, and increased mortality. [8] Therefore, the diagnosis and treatment of PND has become a problem to be solved. ...
Background:
This study aimed to identify predictive biomarkers of perioperative neurocognitive dysfunction (PND) in cerebrospinal fluid of elderly male patients undergoing elective transurethral resection of prostate, using an isobaric tags for relative and absolute quantitative-based quantitative proteomic approach.
Methods:
Patients were evaluated with Mini Mental State Examination at -1 and+3 days of operation. Presence of PND was determined with Z-score method. Patients characteristics and quantitative cerebrospinal fluid proteomes detected with isobaric tags for relative and absolute quantitative-were compared between PND and non-PND patients. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were performed to identify pathways potentially involved in PND.
Result:
A total of 229 patients were included in the study and 32 were diagnosed with PND (incidence 14.4%). The age, incidence of hypertension, and diabetes of PND patients were significantly higher than non-PND patients (P < .05). There were 85 differentially expressed proteins identified, among which High Mobility Group Box 1, prostaglandin D synthase, and matrix metalloproteinase inhibitor were considered to be promising candidates as they might play important roles in pathophysiology of PND.
Conclusion:
Proteomic approach identified potential biomarkers for predicting the occurrence of PND. These findings need to be validated in further studies.
... Despite differences in the clinicopathogenesis of neurodegenerative disorders, tPBM is thought to directly influence mitochondrial dysfunction and oxidative inflammatory processes [13,14]. Neuropathophysiological correlates of Alzheimer's dementia (AD) include, but are not limited to, neurofibrillary tangles; dystrophic neuritis; amyloid precursor protein deposits and increased phosphorylated tau concentrations [13][14][15][16]. The inability for β-amyloid concentrations to be adequately decreased results in the breakdown of microtubular assemblies due to hyperphosphorylated tau. ...
... Because hyperphosphorylation is a signaling process that regulates cell division, abnormalities in microtubules can cause toxicity to cells. Disruptions of the polymerization dynamics of microtubules can result in synaptic failure as these cells are implicated in maintenance of cell structure and homeostatic regulation of cellular metabolic demand [13][14][15][16]. ...
... Because the clinicopathogenesis of neurodegenerative disorders often implicates alterations of neuronal communication between divergent Brodmann areas and functional connectivity networks, the conversion of photons from light therapies may improve cognitive functioning [12]. While comprehensive understanding of the factors that interact to induce the pathognomonic correlates of AD remain elusive, a prominent hypothesis of the etiopathogenesis of AD is related to the brain's inability to adequately produce cellular energy [12][13][14][15][16]. ...
Photobiomodulation (PBM) is the application of light therapy that utilizes photons to alter the activity of molecular and cellular processes in the tissue where the stimulation is applied. Because the photons associated with the therapeutic mechanisms of PBM affect processes associated with the mitochondria, it is hypothesized that PBM increases ATP synthesis. Alteration of the mitochondrial respiratory enzyme, cytochrome c oxidase (CCO), is hypothesized to induce healing to damaged tissues via regeneration. Utilization of PBM has been examined in clinical disorders which include but are not limited to Alzheimer’s/dementia, epilepsy, and age-related macular degeneration. Transcranial PBM (tPBM) utilizes quantum dot light emitting diodes (QLEDs). QLEDs allow for narrow wavelength emissions from applications of PBM to alter electrophysiological activity and tissue regeneration. This chapter aims to evaluate the mechanisms of QLED applications of PBM and its applications as a photodynamic therapy in the medical sciences. Further, this chapter will examine the quantum mechanics of tPBM and its ability to affect electrophysiological activity according to the electroencephalogram (EEG) across the delta, theta, alpha, beta frequency bands.
... Anesthesia and postoperative cognitive dysfunction are closely related to a patient's postoperative recovery (Gaba 2007;Jungwirth et al. 2009). POCD prolongs hospitalization time, increases the cost of perioperative hospitalization, and is associated with increased mortality (Liebert et al. 2016). Related factors include advanced age, surgery, duration of anesthesia and medication, patient's physical condition, and educational level (Peng et al. 2013). ...
Postoperative cognitive dysfunction (POCD) is a major postoperative neurological complication in children and the elderly. However, the detailed mechanisms underlying this process remain unclear. This study aims to investigate the effect of pleiotrophin on sevoflurane-induced neuroinflammation and cognitive impairment. The novel object recognition test was performed to evaluate the cognitive and motor function of aged C57BL/6 (wild-type, WT) and pleiotrophin-knockout mice treated with sevoflurane. Small molecule inhibitors targeting receptor protein tyrosine phosphatase (RPTP) β/ζ, a pleiotrophin receptor, were used to ameliorate cognitive dysfunction. Sevoflurane treatment induced cognitive dysfunction and motor impairment in aged WT mice. Sevoflurane anesthesia induced the upregulation of certain inflammatory cytokines. Pleiotrophin knockout ameliorated the sevoflurane-induced cognitive dysfunction and motor impairment in vivo. Treatment with small molecule inhibitors targeting RPTP β/ζ inhibited sevoflurane-induced neuroinflammation. In summary, pleiotrophin was shown to potentiate sevoflurane anesthesia-induced cognitive dysfunction and learning deficits in mice.
... 89 PBM can also modulate cytoskeleton by modulation of synaptic plasticity in the peripheral 35 and in the central nervous system. 90 Of interest, synaptic plasticity has also been shown to be sexually dimorphic. 91,92 As the cytoskeleton modulation by PBM is responsible for the blockade of neurotransmission 35 seen in the alleviation of the pain in dental extraction and other dental procedures, the gender-specific aspects of the membrane response is an important aspect to take into consideration when optimizing the dose of PBM. ...
Background: The influence of gender is significant in the manifestation and response to many diseases and in the treatment strategy. Photobiomodulation (PBM) therapy, including laser acupuncture, is an evidence-based treatment and disease prevention modality that has shown promising efficacy for a myriad of chronic and acute diseases. Anecdotal experience and limited clinical trials suggest gender differences exist in treatment outcomes to PBM therapy. There is preliminary evidence that gender may be as important as skin color in the individual response to PBM therapy. Aim: To conduct a literature search of publications addressing the effects of gender differences in PBM therapy, including laser acupuncture, to provide a narrative review of the findings, and to explore potential mechanisms for the influence of gender. Methods: A narrative review of the literature on gender differences in PBM applications was conducted using key words relating to PBM therapy and gender. Results: A total of 13 articles were identified. Of these articles, 11 have direct experimental investigations into the response difference in gender for PBM, including laser acupuncture. A variety of cadaver, human, and experimental studies demonstrated results that gender effects were significant in PBM outcome responses, including differences in tendon structural and mechanical outcomes, and mitochondrial gene expression. One cadaver experiment showed that gender was more important than skin tone. The physiologic mechanisms directing gender differences are explored and postulated. Conclusions: The review suggests that to address the requirements of a proficient precision medicine-based strategy, it is important for PBM therapy to consider gender in its treatment plan and dosing prescription. Further research is warranted to determine the correct dose for optimal gender treatment, including gender-specific treatment plans to improve outcomes, taking into account wavelength, energy exposure, intensity, and parameters related to the deliverance of treatment to each anatomical location.
... PBM uses especially red to near-infrared radiation to initiate a cascade of events, whose possible mechanisms of action proposed so far are: -absorption of photons by the first absorbing chromophores, cytochrome c oxidase in mitochondria and non-mitochondrial receptors, such as the ion channels and NADPH oxidase in cell membranes, also with a direct influence on the cellular cytoskeleton [264]. -increased production of ATP, nitric oxide, a sudden outbreak of reactive oxygen species and the modulation of calcium levels. ...
In recent decades, researchers around the world have been studying intensively how micro-organisms that are present inside living organisms could affect the main processes of life, namely health and pathological conditions of mind or body. They discovered a relationship between the whole microbial colonization and the initiation and development of different medical disorders. Besides already known probiotics, novel products such as postbiotics and paraprobiotics have been developed in recent years to create new non-viable micro-organisms or bacterial-free extracts, which can provide benefits to the host with additional bioactivity to probiotics, but without the risk of side effects. The best alternatives in the use of probiotics and postbiotics to maintain the health of the intestinal microbiota and to prevent the attachment of pathogens to children and adults are highlighted and discussed as controversies and challenges. Updated knowledge of the molecular and cellular mechanisms involved in the balance between microbiota and immune system for the introspection on the gut–lung–brain axis could reveal the latest benefits and perspectives of applied photobiomics for health. Multiple interconditioning between photobiomodulation (PBM), probiotics, and the human microbiota, their effects on the human body, and their implications for the management of viral infectious diseases is essential. Coupled complex PBM and probiotic interventions can control the microbiome, improve the activity of the immune system, and save the lives of people with immune imbalances. There is an urgent need to seek and develop innovative treatments to successfully interact with the microbiota and the human immune system in the coronavirus crisis. In the near future, photobiomics and metabolomics should be applied innovatively in the SARS-CoV-2 crisis (to study and design new therapies for COVID-19 immediately), to discover how bacteria can help us through adequate energy biostimulation to combat this pandemic, so that we can find the key to the hidden code of communication between RNA viruses, bacteria, and our body.
