Glutamate and GABA metabolism in transient and permanent middle cerebral artery occlusion in rat:: Importance of astrocytes for neuronal survival
Glutamate and GABA metabolism in transient and permanent middle cerebral artery occlusion in rat:: Importance of astrocytes for neuronal survival
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DOI：
10.1016/j.neuint.2005.12.025
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发表时间：
2006-05-01
影响因子：
4.2
通讯作者：
Sonnewald, U
中科院分区：
文献类型：
--
作者：
Håberg, A;Qu, H;Sonnewald, U
本研究的目的是确定局灶性脑缺血后通过再灌注挽救的脑组织的显着代谢特征。大鼠大脑中动脉闭塞 120 分钟，然后再灌注 120 分钟。大鼠接受[1-C-13]葡萄糖加[1,2-C-13]乙酸的静脉推注。随后，两个大脑区域被认为代表半暗带和缺血核心，即分别是额顶皮质和外侧尾壳核加上下顶叶皮质。用 C-13 NMRS 和 HPLC 进行分析。结果表明，四种代谢事件可区分再灌注半暗带和缺血核心。 (1) [4,5-C-13]谷氨酰胺含量的增加和乙酸盐氧化的改善证明了星形胶质细胞代谢的改善。 (2) 尽管谷氨酸能和 GABA 能神经元中葡萄糖通过丙酮酸脱氢酶进入三羧酸 (TCA) 循环的通量减半，但神经元线粒体活性得到了更好的保留。然而，NAA含量处于对照水平。 (3)谷氨酸能和GABA能神经元使用相对较多的源自丙酮酸羧化酶途径的星形胶质细胞代谢物。 (4) 尽管通过丙酮酸脱氢酶降低了 TCA 循环中的葡萄糖代谢，但乳酸合成并未增加。在缺血核心中，尽管再灌注，神经元和星形细胞TCA循环活性均显着下降。与谷氨酸中的丙酮酸脱氢酶途径相比，源自丙酮酸羧化酶途径的星形胶质细胞前体的利用显着减少，并且在GABA中完全停止。 NAA水平显着下降，乳酸积累。结果表明，星形胶质细胞代谢的保存对于神经元的存活和恢复的预测至关重要。 (C) 2006 Elsevier Ltd. 保留所有权利。
The aim of the present study was to identify the distinguishing metabolic characteristics of brain tissue salvaged by reperfusion following focal cerebral ischemia. Rats were subjected to 120 min of middle cerebral artery occlusion followed by 120 min of reperfusion. The rats received an intravenous bolus injection of [1-C-13]glucose plus [ 1,2-C-13]acetate. Subsequently two brain regions considered to represent penumbra and ischemic core, i.e. the frontoparietal cortex and the lateral caudoputamen plus lower parietal cortex, respectively. were analyzed with C-13 NMRS and HPLC. The results demonstrated four metabolic events that distinguished the reperfused penumbra from the ischemic core. (1) Improved astrocytic metabolism demonstrated by increased amounts of [4,5-C-13]glutamine and improved acetate oxidation. (2) Neuronal mitochondrial activity was better preserved although the flux of glucose via pyruvate dehydrogenase into the tricarboxylic acid (TCA) cycle in glutamatergic and GABAergic neurons was halved. However, NAA content was at control level. (3) Glutamatergic and GABAergic neurons used relatively more astrocytic metabolites derived from the pyruvate carboxylase pathway. (4) Lactate synthesis was not increased despite decreased glucose metabolism in the TCA cycle via pyruvate dehydrogenase. In the ischemic core both neuronal and astrocytic TCA cycle activity declined significantly despite reperfusion. The utilization of astrocytic precursors originating from the pyruvate carboxylase pathway was markedly reduced compared the pyruvate dehydrogenase pathway in glutamate, and completely stopped in GABA. The NAA level fell significantly and lactate accumulated. The results demonstrate that preservation of astrocytic metabolism is essential for neuronal survival and a predictor for recovery. (C) 2006 Elsevier Ltd. All rights reserved.