Resveratrol Provides Neuroprotection By Inhibiting Phosphodiesterases And Regulating The Camp/AMPK/SIRT1 Pathway After Stroke In Rats

Background: Dysfunction of energy metabolism can be a significant and fundamental pathophysiological basis for strokes. In studies of both humans and rodents, resveratrol, a natural polyphenol, has been reported to provide protection from cerebral ischemic injury by regulating expression of silent mating type information regulation 2 homolog 1(SIRT1). However, direct evidence demonstrating that resveratrol exerts neuroprotection from cerebral ischemia injury by decreasing energy consumption is still lacking.Objective: The aim of this study was to elucidate the mechanisms and signaling pathways through which resveratrol regulates energy metabolism in the ischemic brain, and to identify potential targets of resveratrol.Methods: The cerebral ischemia injury of rats was induced by middlecerebral artery occlusion(MCAO). At 24 h after MCAO, an investigator who was blinded to thewhole experiment determined the degree of neurological deficits; TTC staining was used to determine the infarct volume after Res treatment in rats;ATP levels in brain tissues were detected by high performance liquid chromatography; SIRT1 and the phosphorylation of adenosine-monophosphate-activated protein kinase(P-AMPK) expressiones were evaluated by western blot; Levels of phosphodiesterase(PDEs) and cAMP were quantitated by real-time PCR and ELISA, respectively.Results:(1) Resveratrol provides neuroprotection in MCAO rats.(2) Resveratrol increases SIRT1 and p-AMPK expression.(3) Resveratrol might indirectly increase SIRT1 levels by activation of AMPK.(4) Resveratrol promotes restoration of brain tissue ATP levels.(5)A PDE inhibitor increases SIRT1 and p-AMPK expression.( 6) Resveratrol inhibits PDEs and increases cAMP levels.Conclusion: Our findings indicate that resveratrol provides neuroprotection by inhibiting PDEs and regulating the cAMP/AMPK/SIRT1 pathway, which reduces ATP energy consumption during ischemia.