Shimizu H, Graham S H, Chang L H, Mintorovitch J, James T L, Faden A I, Weinstein P R
Department of Neurological Surgery, University of California, San Francisco 94143.
Brain Res. 1993 Mar 5;605(1):33-42. doi: 10.1016/0006-8993(93)91353-t.
The time-course of changes in extracellular glutamate and energy metabolism during 30 or 60 min of complete cerebral ischemia and 60-90 min of reperfusion was investigated by microdialysis and magnetic resonance spectroscopy in parallel groups of rats. During the first 10 min of ischemia, adenosine triphosphate (ATP) was completely depleted, and lactate increased 10-fold; after 30 min, intracellular pH had decreased to 6.33 +/- 0.11. ATP and lactate did not change further between 30 and 60 min of ischemia. Glutamate increased 30-fold between 10 and 30 min of ischemia and continued to increase in the 60-min ischemia group. After 30 min of reperfusion, glutamate had returned to pre-ischemic levels in both groups. The cellular energy state recovered within 50-60 min after 30 min of ischemia but never returned to more than 60% of baseline values after 60 min of ischemia. The continued increase in extracellular glutamate after total depletion of ATP suggests that glutamate release during ischemia is not entirely energy dependent. Ca(2+)-independent glutamate release and failure of energy-dependent glutamate re-uptake mechanisms may result in continued increase in extracellular glutamate. The rapid normalization of extracellular glutamate after 30 and 60 min of ischemia despite differences in the recovery of energy metabolism suggests that the glutamate levels were reduced by an energy-independent mechanism, such as diffusion into the restored circulation.
通过微透析和磁共振波谱技术，在平行分组的大鼠中研究了完全性脑缺血30或60分钟以及再灌注60 - 90分钟期间细胞外谷氨酸和能量代谢变化的时间进程。在缺血的最初10分钟内，三磷酸腺苷（ATP）完全耗尽，乳酸增加了10倍；30分钟后，细胞内pH降至6.33±0.11。在缺血30至60分钟之间，ATP和乳酸没有进一步变化。谷氨酸在缺血10至30分钟之间增加了30倍，并且在60分钟缺血组中继续增加。再灌注30分钟后，两组中的谷氨酸均恢复到缺血前水平。缺血30分钟后，细胞能量状态在50 - 60分钟内恢复，但缺血60分钟后从未恢复到超过基线值的60%。ATP完全耗尽后细胞外谷氨酸持续增加，这表明缺血期间谷氨酸释放并不完全依赖能量。不依赖Ca(2+)的谷氨酸释放以及能量依赖的谷氨酸再摄取机制的失效可能导致细胞外谷氨酸持续增加。尽管能量代谢恢复存在差异，但缺血30和60分钟后细胞外谷氨酸迅速恢复正常，这表明谷氨酸水平是通过一种不依赖能量的机制降低的，例如扩散到恢复的循环中。
