Increased oxidative stress and energy metabolism deficit have been regarded as an important underlying cause for neuronal damage induced by
cerebral ischemia/reperfusion (I/R) injury. In this study, we investigated the oxidative mechanisms underlying the
neuroprotective effects of
resveratrol, a potent
polyphenol antioxidant found in grapes, on structural and biochemical abnormalities in rats subjected to global
cerebral ischemia. Experimental model of transient global
cerebral ischemia was induced in Wistar rats by the four vessel occlusion method for 10 min and followed by different periods of reperfusion. Nissl and
fluoro jade C stained indicated extensive neuronal death at 7 days after I/R. These findings were preceded by a rapid increase in the generation of
reactive oxygen species (ROS),
nitric oxide (NO), lipid peroxidation, as well as by a decrease in Na(+)K(+)-
ATPase activity and disrupted
antioxidant defenses (enzymatic and non-enzymatic) in hippocampus and cortex. Administrating
resveratrol 7 days prior to
ischemia by
intraperitoneal injections (30 mg/kg) significantly attenuated neuronal death in both studied structures, as well as decreased the generation of ROS, lipid peroxidation and NO content. Furthermore,
resveratrol brought
antioxidant and Na(+)K(+)-
ATPase activity in cortex and hippocampus back to normal levels. These results support that
resveratrol could be used as a preventive, or therapeutic, agent in global
cerebral ischemia and suggest that scavenging of ROS contributes, at least in part, to
resveratrol-induced neuroprotection.