Effects of Resveratrol Postconditioning on Cerebral Ischemia in mice: Role of the Sirtuin-1 (SIRT1) Pathway

Abstract

Evidence has demonstrated that resveratrol preconditioning exhibits neuroprotection against cerebral IR injury. The current investigation aimed to explore whether pharmacological postconditioning, by administering resveratrol, after a sustained ischemia prior to prolonged reperfusion abrogates cerebral IR injury. Cerebral ischemia-reperfusion-induced injury mice model was employed in this study to evaluate the neuroprotective effects of pharmacological postconditioning (pPoCo) with resveratrol (30 mg/kg; i.p.) administered 5 mins before reperfusion. We administered Sirtinol, a SIRT1/2 selective inhibitor (10 mg/kg; i.p.) 10 min before ischemia (17 min) and reperfusion (24 h), to elucidate whether the neuroprotection with resveratrol postconditioning depends on SIRT1 activation. Various biochemical, behavioral parameters and histopathological changes were assessed to examine the effect of pPoCo. Infarct size is estimated using TTC staining. It was established that resveratrol postconditioning abrogated the deleterious effects of IR injury expressed with regard to biochemical parameters of oxidative stress (TBARS, SOD, GSH), acetylcholinestrase activity, behavioual parameters (memory, motor coordination), infarct size and histopathological changes. Sirtinol significantly reversed the effect of resveratrol PoCo. We conclude that induced neuroprotective benefits of resveratrol postconditiong may be the consequence of SIRT1 activation and resveratrol can be considered, for further studies, as potential agent inducing pharmacological postconditioning in clinical situations.