Sherwin A L
Montreal Neurological Institute and Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada.
Neurochem Res. 1999 Nov;24(11):1387-95. doi: 10.1023/a:1022580506443.
Studies of neuroactive amino acids and their regulatory enzymes in surgically excised focally epileptic human brain are reviewed. Concentrations of glutamate, aspartate and glycine are significantly increased in epileptogenic cerebral cortex. The activities of the enzymes, glutamate dehydrogenase and aspartate aminotransferase, involved in glutamate and aspartate metabolism are also increased. Polyamine synthesis is enhanced in epileptogenic cortex and may contribute to the activation of N-methyl-D-aspartate (NMDA) receptors. Nuclear magnetic resonance spectroscopy (NMRS) reveals that patients with poorly controlled complex partial seizures have a significant diminution in occipital lobe gamma aminobutyric acid (GABA) concentration. The activity of the enzyme GABA-aminotransaminase (GABA-T) which catalyzes GABA degradation is not altered in epileptogenic cortex. NMRS studies show that vigabatrin, a GABA-T inhibitor and effective antiepileptic, significantly increases brain GABA. Glutamate decarboxylase (GAD), responsible for GABA synthesis, is diminished in interneurons in discrete regions of epileptogenic cortex and hippocampus. In vivo microdialysis performed in epilepsy surgery patients provides measurements of extracellular amino acid levels during spontaneous seizures. Glutamate concentrations are higher in epileptic hippocampi and increase before seizure onset reaching potentially excitotoxic levels. Frontal or temporal cortical epileptogenic foci also release aspartate, glutamate and serine particularly during intense seizures or status epilepticus. GABA in contrast, exhibits a delayed and feeble rise in the epileptic hippocampus possibly due to a reduction in the number and/or efficiency of GABA transporters.
本文综述了对手术切除的局灶性癫痫患者大脑中神经活性氨基酸及其调节酶的研究。致痫性大脑皮层中谷氨酸、天冬氨酸和甘氨酸的浓度显著升高。参与谷氨酸和天冬氨酸代谢的酶，谷氨酸脱氢酶和天冬氨酸转氨酶的活性也有所增加。致痫性皮层中的多胺合成增强，可能有助于N-甲基-D-天冬氨酸（NMDA）受体的激活。核磁共振波谱（NMRS）显示，复杂部分性发作控制不佳的患者枕叶γ-氨基丁酸（GABA）浓度显著降低。催化GABA降解的酶GABA转氨酶（GABA-T）的活性在致痫性皮层中未发生改变。NMRS研究表明，GABA-T抑制剂和有效抗癫痫药物vigabatrin可显著提高脑内GABA水平。负责GABA合成的谷氨酸脱羧酶（GAD）在致痫性皮层和海马体离散区域的中间神经元中减少。在癫痫手术患者中进行的体内微透析可测量自发发作期间细胞外氨基酸水平。癫痫海马体中的谷氨酸浓度较高，且在发作开始前升高，达到潜在的兴奋性毒性水平。额叶或颞叶皮层致痫灶也会释放天冬氨酸、谷氨酸和丝氨酸，尤其是在强烈发作或癫痫持续状态期间。相比之下，癫痫海马体中的GABA升高延迟且微弱，这可能是由于GABA转运体数量和/或效率降低所致。
