Clifford D B, Olney J W, Benz A M, Fuller T A, Zorumski C F
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110.
Epilepsia. 1990 Jul-Aug;31(4):382-90. doi: 10.1111/j.1528-1157.1990.tb05492.x.
Recent evidence implicates the endogenous excitotoxin, glutamate (Glu), in several neurologic disorders, including seizure-related brain damage. Ketamine, phencyclidine, and MK-801, which are noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) subtype of Glu receptor (but do not antagonize kainic acid receptors) were tested in the present study for their effects on behavioral and/or electrographic seizures and seizure-related brain damage induced by kainic acid. Behavioral seizure activity was reduced by these agents, as was spread of electrographic seizures to neocortex, but seizures recorded from deep brain regions such as hippocampus, piriform cortex, and amygdala were not significantly diminished. All three agents prevented seizure-related brain damage in the amygdala, piriform cortex, thalamus, and CA1 region of the hippocampus but conferred little or no protection in the lateral septum and CA3 region of the hippocampus. The regional selectivity of the neuroprotective effect suggests that NMDA receptors may play a more dominant role in seizure-related brain damage in some brain regions than in others. The ability of NMDA antagonists to prevent seizure-related damage in several brain regions without suppressing seizure activity suggests that in these brain regions persistent seizure activity can be maintained by other transmitter systems, with or without NMDA receptor participation, but that seizure-related brain damage is critically dependent on NMDA receptor participation.
最近的证据表明，内源性兴奋性毒素谷氨酸（Glu）与包括癫痫相关脑损伤在内的多种神经系统疾病有关。氯胺酮、苯环己哌啶和MK - 801是谷氨酸受体N - 甲基 - D - 天冬氨酸（NMDA）亚型的非竞争性拮抗剂（但不拮抗 kainic 酸受体），在本研究中测试了它们对由 kainic 酸诱导的行为性和/或脑电图癫痫发作以及癫痫相关脑损伤的影响。这些药物可降低行为性癫痫活动，也可减少脑电图癫痫发作向新皮层的扩散，但来自海马体、梨状皮层和杏仁核等深部脑区的癫痫发作并未显著减少。所有这三种药物均可预防杏仁核、梨状皮层、丘脑和海马体CA1区的癫痫相关脑损伤，但对海马体外侧隔区和CA3区几乎没有或没有提供保护。神经保护作用的区域选择性表明，NMDA受体在某些脑区的癫痫相关脑损伤中可能比在其他脑区发挥更主导的作用。NMDA拮抗剂在不抑制癫痫活动的情况下预防多个脑区癫痫相关损伤的能力表明，在这些脑区，无论有无NMDA受体参与，持续性癫痫活动均可由其他递质系统维持，但癫痫相关脑损伤严重依赖于NMDA受体的参与。
