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BackgroundOur prior study showed that resveratrol could suppress infarct volume and exert neuroprotective effect on rats subjected to focal cerebral ischemia (FCI) injury. Recently, it has been reported in some literature that resveratrol protects the spinal cord, kidney, and heart from ischemia-reperfusion injury through upregulation of nitric oxide (NO). Therefore, this study was designed to investigate the role of nitric oxide on the neuroprotective mechanisms of resveratrol on rats after FCI injury.MethodsThe FCI injury was induced by the middle cerebral artery (MCA) occlusion for 1 hour and then a 24-hour reperfusion followed in the anesthetized Long-Evans rats. Resveratrol was intravenously injected after 1 hour MCA occlusion.ResultsTreatment of resveratrol (0.1 and 1 μg/kg) decreased the lactate dehydrogenase (LDH) in plasma and malondialdehyde (MDA) in FCI injury brain tissue, whereas the level of NO in plasma was increased. In addition, resveratrol downregulated protein and mRNA expression of inducible nitric oxide synthase (iNOS), and upregulated protein and mRNA expression of endothelial nitric oxide synthase (eNOS), while the expression of protein and mRNA of neuronal nitric oxide synthase (nNOS) was unchanged. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, the nonselective NOS inhibitor) or L-N5-(1-iminoethyl)-ornithine (L-NIO, the eNOS selective inhibitor) completely blocked the effect of resveratrol in decreasing infarction volumes.ConclusionsThis study demonstrated the important role of NO in the neuroprotective effect of resveratrol in FCI injury.Clinical RelevanceIschemic brain damage is the major cause of permanent disability in young adults. It has been suggested that up to 80% of all strokes result from ischemic damage in the middle cerebral artery area. The potential for clinical application of pharmacological agents has generated enormous interest in identifying the underlying intracellular signaling pathways and to develop therapeutic strategies that can benefit ischemic stroke injury in patients. This study explored the possible involvement of nitric oxide in neuroprotective effect of resveratrol on focal cerebral ischemia injury.