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 10mg/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 10min global
ischemia. Male Wistar rats were divided into five groups;
sham/saline,
ischemia/saline,
ischemia/1mg/kg RSV,
ischemia/10mg/kg RSV and
sham/10mg/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.