Resveratrol attenuates brain damage in a rat model of focal cerebral ischemia via up-regulation of hippocampal Bcl-2.

A number of studies have demonstrated that resveratrol (Res), a natural polyphenol compound found in plants, shows potent neuroprotective, anti-inflammatory and antioxidant effects; however, its ability to prevent ischemia-induced brain damage remains unclear. Here we tested whether Res played a neuroprotective role in a rat brain ischemia model induced by middle cerebral artery occlusion (MCAO). Adult male rats were randomly assigned into four experimental groups: sham operation (sham), ischemia treatment (MCAO), Res-treated MCAO (Res+MCAO) and Res alone group (Res+sham). The brain damage size and hippocampal apoptotic neurons in each rat were evaluated by triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) staining, respectively. Long-term potentiation (LTP) induced by high-frequency stimulation (HFS) in the hippocampus was assessed with extracellular recording. The expression of apoptosis-related proteins, i.e., Bcl-2 and Bax, in the hippocampus was detected by western blot. Our results revealed that Res treatment significantly reduced brain infarct volume of MCAO rats as compared to MCAO rats without Res treatment. A significant increase in TUNEL-positive neurons in the hippocampal CA1 region was visualized in the MCAO rats as compared to that of the sham group, but this increase was attenuated with Res treatment. Functionally, extracellular recordings revealed that MCAO operation impaired LTP in the hippocampal CA1 region and the basal synaptic transmission between the Schaffer collaterals, whereas Res treatment rescued the impaired LTP and facilitated synaptic transmission in the CA1 region of the MCAO rats. Res treatment increased the expression of anti-apoptotic protein Bcl-2 and decreased the expression of pro-apoptotic protein Bax in the MCAO rats. The findings suggest that Res can attenuate the deleterious effects of focal cerebral ischemia/reperfusion-induced brain injury and function as a potential neuroprotective agent. The neuroprotective qualities of Res, based on our data, may be attributable to the up-regulation of Bcl-2 expression and down-regulation of Bax expression.