Effect of pinealectomy and melatonin replacement on morphological and biochemical recovery after traumatic brain injury.
ABSTRACT Numerous studies showed that melatonin, a free radical scavenger, is neuroprotective. In this study, we investigated the effect of pinealectomy and administration of exogenous melatonin on oxidative stress and morphological changes after experimental brain injury. The animals were divided into six groups, each having 12 rats. Group 1 underwent craniotomy alone. Group 2 underwent craniotomy followed by brain trauma and received no medication. Group 3 underwent craniotomy followed by brain trauma and received melatonin. Group 4 underwent pinealectomy and craniotomy alone. Group 5 underwent pinealectomy and craniotomy followed by brain injury and received no medication. Group 6 underwent pinealectomy and craniotomy followed by brain trauma and received melatonin. Melatonin (100 mg/kg) was given intraperitoneally immediately after trauma to the rats in Groups 3 and 6. Pinealectomy caused a significant increase in the malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), and xanthine oxidase (XO) levels, and a decrease in GSH levels as compared to the control group. Trauma to pinealectomized rats causes significantly higher oxidative stress. Exogeneous melatonin administration significantly reduced MDA, XO and NO levels, increased GSH levels, and attenuated tissue lesion area. These findings suggest that reduction in endogenous melatonin after pinealectomy makes the rats more vulnerable to trauma, and exogenous melatonin administration has an important neuroprotective effect.
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ABSTRACT: Traumatic brain injury (TBI) is frequently associated with abnormal blood-brain barrier function, resulting in the release of factors that can be used as molecular biomarkers of TBI, among them GFAP, UCH-L1, S100B, and NSE. Although many experimental studies have been conducted, clinical consolidation of these biomarkers is still needed to increase the predictive power and reduce the poor outcome of TBI. Interestingly, several of these TBI biomarkers are oxidatively modified to carbonyl groups, indicating that markers of oxidative stress could be of predictive value for the selection of therapeutic strategies. Some drugs such as corticosteroids and progesterone have already been investigated in TBI neuroprotection but failed to demonstrate clinical applicability in advanced phases of the studies. Dietary antioxidants, such as curcumin, resveratrol, and sulforaphane, have been shown to attenuate TBI-induced damage in preclinical studies. These dietary antioxidants can increase antioxidant defenses via transcriptional activation of NRF2 and are also known as carbonyl scavengers, two potential mechanisms for neuroprotection. This paper reviews the relevance of redox biology in TBI, highlighting perspectives for future studies.BioMed research international. 01/2014; 2014:723060.
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ABSTRACT: OBJECTIVE. The purpose of this study was to determine if there is an association between tentorial length and angle and sleep-wake disturbances in patients with mild traumatic brain injury (TBI). MATERIALS AND METHODS. MRI examinations of the brain of 34 consecutive patients with mild TBI with sleep-wake disturbance and 30 patients with mild TBI without sleep-wake disturbance were retrospectively reviewed. The length of the tentorium on a sagittal T1-weighted image (tentorial length) and the angle formed between the tentorium and a line through the foramen magnum (tentorial angle) were measured. Results were correlated with both neuropsychologic testing and any sleep-wake disturbance. RESULTS. No significant difference existed between patients with and without sleep-wake disturbances in terms of age (p = 0.44), sex (p = 0.13), Immediate Post-Concussion Assessment Cognitive Test total symptom score (p = 0.10), verbal memory score (p = 0.32), visual memory score (p = 0.31), processing speed (p = 0.15), or reaction time (p = 0.84). Tentorial length in patients with mild TBI with sleep-wake disturbances was significantly longer than patients with mild TBI without sleep-wake disturbances (p < 0.01), and tentorial angle was significantly smaller (p < 0.01). Tentorial angle was inversely correlated with length of time to recovery (p = 0.002), and tentorial length was directly correlated with length of time to recovery (p < 0.001). CONCLUSION. Among patients with mild TBI with similar cognitive function and symptom severity, those with sleep-wake disturbances have significantly longer tentorial length with a flatter angle than do patients with mild TBI without sleep symptoms, with length of time to recovery being directly correlated with tentorial length and indirectly correlated with tentorial angle. Direct impact between the tentorium and the pineal gland during mild TBI may lead to pineal gland injury, disruption of melatonin homeostasis, and sleep-wake disturbances.American Journal of Roentgenology 03/2014; 202(3):614-8. · 2.90 Impact Factor
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ABSTRACT: Alzheimer's disease is associated to impairments of learning and memory. Because studies demonstrated that erythropoietin has positive effects on central nervous system, the aim of this study was to evaluate the effect of erythropoietin on spatial learning and memory in a well defined model for Alzheimer's disease. Rat model of Alzheimer's was created by injecting streptozotocin in lateral ventricles of the brain. Two weeks later, the rats were assessed through passive avoidance learning test to confirm the induction of Alzheimer's. After that, they received erythropoietin (5000IU/kg) every other day, for two weeks and then spatial learning and memory were assessed by a 5-day protocol of Morris water maze test in them. The results showed that streptozotocin severely damaged learning and memory in rats. Erythropoietin had no significant effect in the control rats; however, it significantly improved learning and memory in rats with Alzheimer's disease, as the task performance of the rats treated with erythropoietin was like the control group. The results suggest that erythropoietin can be considered as an effective treatment for neurodegenerative damages.Pathophysiology 04/2013;