Resveratrol protects CA1 neurons against focal cerebral ischemic reperfusion-induced damage via the ERK-CREB signaling pathway in rats

• In this study, we found that Res pretreatment could prevent the focal cerebral ischemia-induced neuronal death and cognitive injury.
• NMDA receptor mediated ERK-CREB signaling pathway may be involved in Res-induced neuroprotection following focal cerebral ischemia.
• These findings suggest that Res might serve as a potential therapeutic compound for preventing and treating neuronal dysfunctions as well as cognitive deficits caused by focal cerebral ischemia and stroke.

Ischemic stroke is a primary cause of mortality and disability in the aged population. Resveratrol (Res), a natural polyphenol enriched in plants, presents diverse biological activities, e.g., antiinflammatory and anti-oxidation effects. Here, we evaluated whether Res pretreatment influenced focal cerebral ischemia-induced cognitive impairment, and we explored the underlying mechanisms in rats. The results showed that a single administration of Res (30 mg/kg, i.p.) at 1 or 4 h, but not at 24 h before focal cerebral ischemia exerted significant neuroprotective effects, including a reduction in hippocampal CA1 neuronal death and spatial cognition deficits caused by ischemia. The neuroprotective effects of Res were suppressed by pretreatment with MK801, an NMDA receptor blocker, or U0126, an extracellular signal regulated kinase 1/2 (ERK1/2) kinase inhibitor. A western blot analysis revealed that Res treatment at 1 h before ischemia significantly increased ERK1/2 phosphorylation and cyclic-AMP response element binding protein (CREB) phosphorylation in the CA1 region of the hippocampus, which can be prevented with U0126 pretreatment. The results showed that the NMDA receptor-mediated ERK-CREB signaling pathway might participates in Res-induced neuroprotection in rats with focal cerebral ischemia.