Neuroprotective effects of resveratrol on ischemic injury mediated by improving brain energy metabolism and alleviating oxidative stress in rats

In this study, we investigated whether resveratrol could protect against ischemic injury by improving brain energy metabolism and alleviating oxidative stress. Male rats were divided into three groups: sham operation, ischemia treatment, and ischemia combined with resveratrol treatment (resveratrol-treated group, 30 mg/kg intraperitoneally for 7 days). Cerebral ischemia was induced by using the model of middle cerebral artery occlusion. The dialysates in hypothalamus were obtained by brain microdialysis technique. The effects of resveratrol on neurologic functions and histopathologic changes were evaluated. The levels of ATP, ADP, AMP, adenosine, inosine, hypoxanthine and xanthine in microdialysate were monitored by HPLC analysis. The levels of malondialdehyde and the activities of xanthine oxidase in brain tissues were analyzed in three groups. This study shows that the ischemic infarcts were significantly reduced and neurological functions were improved in resveratrol-treated group compared to ischemia group. The analysis results show that resveratrol treatments remarkably enhanced the level of glucose, ATP and energy charge; decreased the levels of lactate during I/R period. Resveratrol treatments significantly increased the basal levels of adesonine and inosine, inhibited the elevations of hypoxanthine and xanthine levels and remarkably decreased xanthine oxidase activity and malondialdehyde levels. This study provides in vivo evidence that resveratrol could exert neuroprotective effect against ischemia injury by improving brain energy metabolism and alleviating oxidative stress via inhibiting xanthine oxidase activity and preventing the production of hypoxanthine, xanthine and oxygen radicals during ischemia/reperfusion.