The present study was carried out to elucidate the neuroprotective effect and influence of resveratrol on the extracellular levels of neurotransmitter and neuromodulator during ischemia/reperfusion in rats. Male rats were divided into three groups: sham operation, ischemia treatment, and ischemia combined with resveratrol treatment (resveratrol-treated group, 30 mg/kg intraperitoneally for 7 days). Cerebral ischemia was induced by using the model of middle cerebral artery occlusion. The dialysates in hypothalamus were obtained by brain microdialysis technique. The levels of sixteen amino acids and amines in microdialysate were monitored by capillary electrophoresis analysis. This study shows that the ischemic infarcts were significantly reduced and neurological functions were improved in resveratrol-treated group compared to ischemia group. The analysis results demonstrate that chronic treatment with resveratrol remarkably reduced the release of excitatory neurotransmitter glutamate, aspartate and neuromodulator d-Serine during ischemia and reperfusion; and significantly increased the basal extracellular levels of inhibitory neurotransmitter γ-amino-n-butyric acid, glycine and taurine. Chronic treatment with resveratrol also ameliorated O-phosphoethanolamine levels and excitotoxic index during ischemia and reperfusion. This study provides the first in vivo evidence that resveratrol could exert neuroprotective effect against ischemia injury by modulating the release of multiple neurotransmitters and neuromodulators during ischemia/reperfusion.

In this work, focal cerebral ischemia/reperfusion was induced by the model of middle cerebral artery occlusion. The dialysates of extracellular fluid in hypothalamus were obtained by using brain microdialysis technique. An efficient and sensitive chiral capillary electrophoresis with laser-induced fluorescence detection procedure was developed for the simultaneous determination of multiple amino acids neurotransmitter including Arg, Lys, Trp, GABA, l-Ser, Ala, Tau, Gly, Glu and Asp; catcholamine (dopamine) and neuromodulator (d-Ser and O-phosphoethanolamine) in microdialysate. Different parameters that influenced CE separation were optimized. The optimal method was used to investigate the dynamic changes of neurotransmitters and neuromodulators during cerebral ischemia/reperfusion. The results indicated that extracellular levels of multiple neurotransmitters and neuromodulators were elevated during cerebral ischemia/reperfusion. The dynamic changes and functional status of releasable neurotransmitters and neuromodulators during ischemia/reperfusion were discussed.