Resveratrol downregulates type-1 glutamate transporter expression and microglia activation in the hippocampus following cerebral ischemia reperfusion in rats

The naturally occurring polyphenol phytoalexin resveratrol (RSV) regulates neuronal inflammation in various disease models and protects the brain against ischemic injury. Cell surface glutamate transporters on perisynaptic astrocytes are important regulators of extracellular glutamate levels and synaptic activation. Following cerebral ischemia, reduced astroglial type-1 glutamate transporter (GLT-1) expression in the CA1 pyramidal layers of the hippocampus contribute to neurotoxic glutamate levels. The current study examined the effects of 21-day RSV pretreatment (1 or 10 mg/kg dose; i.p.) on microglia and astrocyte activation and characterized GLT-1 expression in the dentate gyrus (DG), CA1 and CA3 layers of the hippocampus 7 days following 10 min global ischemia. Male Wistar rats were divided into five groups; sham/saline, ischemia/saline, ischemia/1 mg/kg RSV, ischemia/10 mg/kg RSV and sham/10 mg/kg RSV. Immunohistochemical detection of GLT-1, CD11b/c, glial fibrillary acidic protein (GFAP) assessed type 1 glutamate transporter expression and microglial/glial cell activation following sham surgery or global ischemia. Our findings demonstrate prevention by RSV of ischemia-induced reduction of GLT-1 expression in the vulnerable CA1 layer 7 days following global ischemia, which was accompanied by the polyphenol's inhibition of post ischemic increase in CD11b/c and GFAP expression. RSV also conferred significant CA1 neuronal protection positively correlated with attenuation of glutamate transporter activation. These findings support beneficial effects of RSV in modulation of the excitotoxic cascade postischemia, which are congruent with anti-inflammatory effects observed in various pathological models. (C) 2015 Elsevier B.V. All rights reserved.