title: Resveratrol protects CA1 neurons against focal cerebral ischemic reperfusion-induced damage via the ERK-CREB signaling pathway in rats.
abstract: 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 (30mg/kg, i.p.) at 1 or 4h, but not at 24h 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 1h 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.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China; Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China; Pharmacy Intravenous Admiture Services, Binhu Hospital of Hefei, Anhui Medical University, Hefei, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: College of Stomatology, Anhui Medical University, Hefei, China.
authors.forename: Yuanyin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China; Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China. Electronic address: wangliecheng@ahmu.edu.cn.
authors.forename: Liecheng
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D002544:Cerebral Infarction / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D003071:Cognition / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000150:complications / Q000517:prevention & control; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D002070:Butadienes; D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D009570:Nitriles; D016194:Receptors, N-Methyl-D-Aspartate; D013267:Stilbenes; C113580:U 0126; D016291:Dizocilpine Maleate; D048049:Extracellular Signal-Regulated MAP Kinases; D000077185:Resveratrol
keywords: Cell signaling; Cerebral ischemia; Hippocampus; Learning and memory; Neuroprotection; Resveratrol