Håberg A, Qu H, Sonnewald U
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Neurochem Int. 2006 May-Jun;48(6-7):531-40. doi: 10.1016/j.neuint.2005.12.025. Epub 2006 Feb 28.
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-(13)C]glucose plus [1,2-(13)C]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 (13)C 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-(13)C]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.
本研究的目的是确定局灶性脑缺血后再灌注挽救的脑组织的独特代谢特征。将大鼠大脑中动脉闭塞120分钟，随后再灌注120分钟。大鼠接受静脉推注[1-(13)C]葡萄糖加[1,2-(13)C]乙酸盐。随后，分别用(13)C核磁共振波谱法（(13)C NMRS）和高效液相色谱法（HPLC）分析被认为代表半暗带和缺血核心的两个脑区，即额顶叶皮质和外侧尾壳核加顶叶下部皮质。结果显示了四个代谢事件，这些事件区分了再灌注后的半暗带和缺血核心。(1) 星形胶质细胞代谢改善，表现为[4,5-(13)C]谷氨酰胺含量增加和乙酸氧化改善。(2) 神经元线粒体活性得到更好的保留，尽管在谷氨酸能和γ-氨基丁酸能（GABA能）神经元中，通过丙酮酸脱氢酶进入三羧酸（TCA）循环的葡萄糖通量减半。然而，N-乙酰天门冬氨酸（NAA）含量处于对照水平。(3) 谷氨酸能和GABA能神经元相对更多地利用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在TCA循环中的葡萄糖代谢减少，但乳酸合成并未增加。在缺血核心，尽管再灌注，神经元和星形胶质细胞的TCA循环活性均显著下降。与谷氨酸中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明显减少，在GABA中则完全停止。NAA水平显著下降，乳酸积累。结果表明，星形胶质细胞代谢的保留对神经元存活至关重要，并且是恢复的预测指标。
