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Background: The incidence of cerebral ischemia disease leading cause of death in human population worldwide. Treatment of cerebral ischemia remains a clinical challenge for researchers and mechanisms of cerebral ischemia remain unknown. During the cerebral ischemia, inflammatory reaction and oxidative stress plays an important role. The current investigation scrutinized the neuroprotective and anti-inflammatory role of pterostilbene against cerebral ischemia in middle cerebral artery occlusion (MCAO) rodent model and explore the underlying mechanism.Methods: The rats were divided into following groups viz., normal, sham, MCAO and MCAO + pterostilbene (25 mg/kg) group, respectively. The groups received the oral administration of pterostilbene for 30 days followed by MCAO induction. The neurological score, brain water content, infarct volume and Evan blue leakage were estimated. Hepatic, renal, heart, inflammatory cytokines and inflammatory mediators were estimated.Results: Pterostilbene treatment significantly (p < 0.001) improved the body weight and suppressed the glucose level and brain weight. Pterostilbene significantly (p < 0.001) reduced the hepatic, renal and heart parameters. Pterostilbene significantly (p < 0.001) decreased the level of glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and decreased the level of malonaldehyde (MDA), 8-Hydroxy-2′-deoxyguanosine (8-OHdG). Pterostilbene significantly (p < 0.001) inflammatory cytokines and inflammatory parameters such as cyclooxygenase-2 (COX-2), inducible nitric oxidase synthase (iNOS) and prostaglandin (PGE2). Pterostilbene significantly (p < 0.001) down-regulated the level of metalloproteinases (MMP) such as MMP-2 and MMP-9. Pterostilbene suppressed the cellular swelling, cellular disintegration, macrophage infiltration, monocyte infiltration and polymorphonuclear leucocyte degranulation in the brain.Conclusion: In conclusion, Pterostilbene exhibited the neuroprotective effect against cerebral ischemia in rats via anti-inflammatory mechanism.

Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients who undergo surgery involving anesthesia. Its underlying mechanisms remain unclear. Autophagy plays an important role in the damage and repair of the nervous system and is associated with the development of POCD. Using a rat model, adenosine monophosphate-activated protein kinase α1 (AMPKα1), an important autophagy regulator, was found to be significantly downregulated in rats with POCD that was induced by sevoflurane anesthesia or by appendectomy. Overexpression of AMPKα1-ameliorated POCD, as indicated by decreased escape latencies and increased target quadrant swimming times, swimming distances, and platform crossing times during Morris water maze tests. AMPKα1 overexpression activated autophagy signals by increasing the expression of light chain 3 II (LC3-II) and Beclin1 and decreasing the expression of p62 in the hippocampus of rats with POCD. Moreover, blocking autophagy by 3-methyladenine partly attenuated AMPKα1-mediated POCD improvement. Furthermore, overexpression of AMPKα1 could upregulate the expression of p-AMPK and Sirt1 in the hippocampus of rats with POCD. Intriguingly, inhibiting AMPK signals via Compound C effectively attenuated AMPKα1-mediated POCD improvement, concomitant with the downregulation of p-AMPK, Sirt1, LC3-II, and Beclin1 and the upregulation of p62. We thus concluded that overexpression of AMPKα1 can improve POCD via the AMPK-Sirt1 and autophagy signaling pathway.