Pascual J M, Carceller F, Roda J M, Cerdán S
Servicio de Neurocirugía, Hospital La Paz, Madrid, Spain.
Stroke. 1998 May;29(5):1048-56; discussion 1056-7. doi: 10.1161/01.str.29.5.1048.
Even though the utilization of substrates alternative to glucose may play an important role in the survival of brain cells under ischemic conditions, evidence on changes in substrate selection by the adult brain in vivo during ischemic episodes remains very limited. This study investigates the utilization of glutamate, glutamine, and GABA as fuel by the neuronal and glial tricarboxylic acid cycles of both cerebral hemispheres after partially reversible focal cerebral ischemia (FCI).
Right hemisphere infarct was induced in adult Long-Evans rats by permanent occlusion of the right middle cerebral artery and transitory occlusion of both common carotid arteries. (1,2-13C2) acetate was infused for 60 minutes in the right carotid artery immediately after carotid recirculation had been re-established (1-hour group) or 23 hours later (24-hour group). Extracts from both cerebral hemispheres were prepared and analyzed separately by 13C nuclear magnetic resonance and computer-assisted metabolic modeling.
FCI decreased the oxidative metabolism of glucose in the brain in a time-dependent manner. Reduced glucose oxidation was compensated for by increased oxidations of (13C) glutamate and (13C) GABA in the astrocytes of the ipsilateral hemispheres of both groups. Increased oxidative metabolism of (13C) glutamine in the neurons was favored by increased activity of the neuronal pyruvate recycling system in the 24-hour group.
Data were obtained consistent with time-dependent changes in the utilization of glutamate and GABA or glutamine as metabolic substrates for the glial or neuronal compartments of rat brain after FCI.
尽管在缺血条件下，利用葡萄糖以外的底物可能对脑细胞存活起着重要作用，但关于成体大脑在缺血发作期间体内底物选择变化的证据仍然非常有限。本研究调查了部分可逆性局灶性脑缺血（FCI）后，大脑两半球神经元和胶质细胞三羧酸循环对谷氨酸、谷氨酰胺和GABA作为燃料的利用情况。
通过永久性闭塞右侧大脑中动脉和暂时性闭塞双侧颈总动脉，在成年Long-Evans大鼠中诱导右侧半球梗死。在恢复颈动脉再灌注后立即（1小时组）或23小时后（24小时组），经右侧颈动脉注入（1,2-13C2）乙酸盐60分钟。分别制备大脑两半球的提取物，并通过13C核磁共振和计算机辅助代谢建模进行分析。
FCI以时间依赖性方式降低了大脑中葡萄糖的氧化代谢。两组同侧半球星形胶质细胞中（13C）谷氨酸和（13C）GABA氧化增加，补偿了葡萄糖氧化的减少。24小时组神经元丙酮酸循环系统活性增加，有利于（13C）谷氨酰胺在神经元中的氧化代谢增加。
获得的数据与FCI后大鼠大脑胶质或神经元区室将谷氨酸、GABA或谷氨酰胺作为代谢底物的利用情况随时间变化一致。
