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大脑中动脉闭塞后Wistar大鼠和Fischer 344大鼠纹状体细胞外氨基酸浓度的差异。

Differences in striatal extracellular amino acid concentrations between Wistar and Fischer 344 rats after middle cerebral artery occlusion.

作者信息

Herz R C, Gaillard P J, de Wildt D J, Versteeg D H

机构信息

Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University, The Netherlands.

出版信息

Brain Res. 1996 Apr 9;715(1-2):163-71. doi: 10.1016/0006-8993(95)01572-8.

Abstract

We hypothesized that the interstrain difference between Wistar and Fischer-344 (F344) rats in cerebral infarction volume after proximal middle cerebral artery (MCA) occlusion might be explained by differences in excitotoxicity between both rat strains. Using microdialysis we measured during a 5 h period after MCA occlusion the release of aspartate, glutamate and taurine in the cerebral cortex and the striatum. The volume of striatal infarction was comparable in Wistar and F344 rats. We found, however, in Wistar rats a significantly higher striatal efflux of aspartate and glutamate than in F344 rats, whereas the striatal taurine efflux was of a similar magnitude in the two strains. Because of the (variably) smaller volume of cortical infarction in Wistar rats (than that in F344), the location of the microdialysis probe-membrane with respect to the area of cortical infarction differed between Wistar rats. Hence, a reliable comparison between the quantitative amount of amino acids in the dialysate from the cortical probes of both rat strains could not be made. These results, demonstrating differences in striatal excitotoxicity between Wistar and F344 rats after MCA occlusion, are the first to show interstrain differences in striatal pathophysiology of focal ischemia between these normotensive rat strains. They do however not explain why MCA occlusion results in a significantly different volume of cortical infarction between Wistar and F344 rats. The F344 strain will probably show in a more sensitive way, as compared to Wistar rats, neuroprotective effects of agents that diminish excitotoxic damage during focal cerebral ischemia.

摘要

我们推测,Wistar大鼠和Fischer-344(F344)大鼠在大脑中动脉(MCA)近端闭塞后脑梗死体积的品系间差异,可能是由于这两种大鼠品系在兴奋性毒性方面的差异所致。我们采用微透析技术,在MCA闭塞后的5小时内,测量了大脑皮层和纹状体中天冬氨酸、谷氨酸和牛磺酸的释放量。Wistar大鼠和F344大鼠的纹状体梗死体积相当。然而,我们发现,Wistar大鼠纹状体中天冬氨酸和谷氨酸的流出量显著高于F344大鼠,而两种品系中纹状体牛磺酸的流出量大小相似。由于Wistar大鼠皮层梗死体积(比F344大鼠)(变化地)较小,Wistar大鼠中微透析探针膜相对于皮层梗死区域的位置有所不同。因此,无法对两种大鼠品系皮层探针透析液中氨基酸的定量进行可靠比较。这些结果表明,MCA闭塞后Wistar大鼠和F344大鼠在纹状体兴奋性毒性方面存在差异,首次显示了这些正常血压大鼠品系在局灶性缺血纹状体病理生理学方面的品系间差异。然而,它们并未解释为什么MCA闭塞在Wistar大鼠和F344大鼠之间会导致显著不同的皮层梗死体积。与Wistar大鼠相比,F344品系可能会更敏感地显示出在局灶性脑缺血期间减少兴奋性毒性损伤的药物的神经保护作用。

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