An ischemia/reperfusion injury of rat’s sciatic nerve was experimentally developed. In this model, we measured the in vivo production of superoxide radical, as a marker of oxidative stress and the occludin expression as an indicator of blood-nerve barrier function and we examined potential protective innervations against these abnormalities. Right sciatic nerves of the animals underwent 3 h of ischemia followed by 7 days of reperfusion and were divided into three groups: ischemic, pretreated with vitamin C in conjunction with vitamin E and treated with tissue plasminogen activator. Compared to measurements from left sciatic nerves used as sham, the ischemic group showed significantly increased superoxide radical and reduced expression of occludin in western blot and immunohistochemistry. No such differences were detected between sham and nerves in the vitamin or tissue plasminogen activator groups. It is suggested that the experimental ischemia/reperfusion model was suitable for studying the relationship between oxidative state and blood-nerve barrier. The reversion of abnormalities by the applied neuroprotective agents might prove to be a clinically important finding in view of the implication of vascular supply derangement in various neuropathies in humans.

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Its high metabolic rate and high polyunsaturated fatty acid content make the brain very sensitive to oxidative damage. In the brain, neuronal metabolism occurs at a very high rate and generates considerable amounts of reactive oxygen species and free radicals, which accumulate inside neurons, leading to altered cellular homeostasis and integrity and eventually irreversible damage and cell death. A misbalance in redox metabolism and the subsequent neurodegeneration increase throughout the course of normal aging, leading to several age-related changes in learning and memory as well as motor functions. The neuroprotective function of antioxidants is crucial to maintain good brain homeostasis and adequate neuronal functions. Vitamins E and C are two important antioxidants that are taken up by brain cells via the specific carriers αTTP and SVCT2, respectively. The aim of this study was to use immunohistochemistry to determine the distribution pattern of these vitamin transporters in the brain in a mouse model that shows fewer signs of brain aging and a higher resistance to oxidative damage. Both carriers were distributed widely throughout the entire brain in a pattern that remained similar in 4-, 12-, 18- and 24-month-old mice. In general, αTTP and SVCT2 were located in the same regions, but they seemed to have complementary distribution patterns. Double-labeled cell bodies were detected only in the inferior colliculus, entorhinal cortex, dorsal subiculum, and several cortical areas. In addition, the presence of αTTP and SVCT2 in neurons was analyzed using double immunohistochemistry for NeuN and the results showed that αTTP but not SVCT2 was present in Bergmann’s glia. The presence of these transporters in brain regions implicated in learning, memory and motor control provides an anatomical basis that may explain the higher resistance of this animal model to brain oxidative stress, which is associated with better motor performance and learning abilities in old age.

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Acute exposure to high doses of glucocorticoids (GCs) may potentially increase the basal levels of reactive oxygen species (ROS) by altering the defence capacity against oxidative damage. Also, antioxidants may affect the oxidative breakdown of tissues. Therefore, the aim of this work was to determine the effects of dietary intake vitamin E and selenium (Se) on lipid peroxidation (LPO) as thiobarbituric acid reactive substances (TBARS) and on the antioxidative defence mechanisms in the brain of rats treated with high doses of prednisolone. Two hundred and fifty adult male Wistar rats were randomly divided into five groups. The rats were fed a normal diet, but groups 3, 4, and 5 received a daily supplement in their drinking water of 20mg vitamin E, 0.3mg Se, and a combination of vitamin E and Se, respectively, for 30days. For 3days subsequently, the control (group 1) was treated with a placebo, and the remaining 4 groups were injected intramuscularly with 100mg/kg body weight (bw) prednisolone. After the last administration of prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48h and the activities of enzymes selenium-glutathione peroxidase (Se-GSH-Px) and catalase (CAT), and the levels of reduced glutathione (reduced GSH) and TBARS in their brains were measured. Se-GSH-Px and CAT enzyme activities, and reduced GSH levels in the prednisolone treatment group (group 2) began to decrease gradually at 4h (p<0.01, p<0.05, respectively), falling respectively to 60, 50, and 40% of the control levels by 24h (p<0.001, p<0.01), and recovering to the control levels at 48h. In contrast, prednisolone administration caused an increase in the brain TBARS, reaching up to six times the level of the control at 24h (p<0.001). However, supplementation with vitamin E and Se had a preventive effect on the elevation of the brain TBARS and improved the diminished activities of antioxidative enzymes and the levels of reduced GSH. Therefore, the present study attempts to determine the sequence of cellular membrane damage in the brain of the rats after high doses GC administration and the possible roles in vivo of vitamin E and Se, and their combination.

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