Abstract
Polyphenol resveratrol (RSV) has been associated with Silent Information Regulator T1 (SIRT1) and AMP-activated protein kinase (AMPK) metabolic stress sensors and probably responds to the intracellular energy status. Our purpose is to investigate the neuroprotective effects of RSV and the association with SIRT1 and AMPK signaling in recurrent ischemia models. In this study, elderly male Wistar rats received a combination of two mild transient Middle Cerebral Artery Occlusions (tMCAO) as in vivo recurrent ischemic model. Primary cultured cortical neuronal cells subjected to combined oxygen–glucose deprivation (OGD) were used as in vitro recurrent ischemic model. RSV administration significantly reduced infarct volumes, improved behavioral deficits and protected neuronal cells from cell death in recurrent ischemic stroke models in vivo and in vitro. RSV treatments significantly increased the intracellular NAD+/NADH ratio, AMPK and SIRT1activities, decreased energy assumption and restored cell energy ATP level. SIRT1 and AMPK inhibitors and specific siRNA for SIRT1 and AMPK significantly abrogated the neuroprotection induced by RSV. AMPK-siRNA and inhibitor decreased SIRT1 activities; however, SIRT1-siRNA and inhibitor had no impact on p-AMPK levels. These results indicated that the neuroprotective effects of RSV increased the intracellular NAD+/NADH ratio as well as AMPK and SIRT1 activities, thereby reducing energy ATP requirements during ischemia. SIRT1 is a downstream target of p-AMPK signaling induced by RSV in the recurrent ischemic stroke model.

Keywords
RSV NeuroprotectionRecurrent Stroke ModelSIRT1 and AMPK signalingIntracellular NAD+/NADH ratio Intracellular ATP level

Cite this paper
houjun Zheng, Ke Ma, Xiao-Ji Wang, Li-Mei Wang, A dietary polyphenol resveratrol acts to provide neuroprotection in recurrent stroke models by reducing energy requirements during ischemia , SCIREA Journal of Clinical Medicine. Volume 1, Issue 1, October 2016 | PP. 12-37.

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