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

机译:白藜芦醇下调大鼠脑缺血再灌注后海马中1型谷氨酸转运蛋白的表达和小胶质细胞的激活

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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.
机译:天然存在的多酚植物抗毒素白藜芦醇(RSV)调节各种疾病模型中的神经元炎症,并保护大脑免受缺血性损伤。突触周围星形胶质细胞上的细胞表面谷氨酸转运蛋白是细胞外谷氨酸水平和突触激活的重要调节剂。脑缺血后,海马CA1锥体层中星形胶质1型谷氨酸转运蛋白(GLT-1)的表达降低,有助于神经毒性谷氨酸水平。当前研究检查了21天RSV预处理(1或10 mg / kg剂量;腹膜内)对小胶质细胞和星形胶质细胞活化的影响,并表征了海马齿状回(DG),CA1和CA3层中GLT-1的表达7全球缺血10分钟后的几天。将雄性Wistar大鼠分成五组。假/盐水,局部缺血/生理盐水,局部缺血/ 1 mg / kg RSV,局部缺血/ 10 mg / kg RSV和深部/ 10 mg / kg RSV。假手术或全身缺血后,GLT-1,CD11b / c,神经胶质纤维酸性蛋白(GFAP)的免疫组织化学检测评估了1型谷氨酸转运蛋白的表达和小胶质/神经胶质细胞的活化。我们的发现表明,通过RSV预防局部缺血后7天局部缺血诱导的CA1层中GLT-1表达的降低,并伴有多酚对CD11b / c和GFAP表达的局部缺血后增加的抑制作用。 RSV还赋予了显着的CA1神经元保护,与谷氨酸转运蛋白激活的减弱呈正相关。这些发现支持RSV在调节兴奋性毒性级联缺血后的有益作用,这与在各种病理模型中观察到的抗炎作用是一致的。 (C)2015 Elsevier B.V.保留所有权利。

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