KETAMINE, PHENCYCLIDINE, AND MK-801 PROTECT AGAINST KAINIC ACID-INDUCED SEIZURE-RELATED BRAIN-DAMAGE
KETAMINE, PHENCYCLIDINE, AND MK-801 PROTECT AGAINST KAINIC ACID-INDUCED SEIZURE-RELATED BRAIN-DAMAGE
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DOI：
10.1111/j.1528-1157.1990.tb05492.x
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发表时间：
1990-07-01
期刊：
影响因子：
5.6
通讯作者：
ZORUMSKI, CF
中科院分区：
文献类型：
--
作者：
CLIFFORD, DB;OLNEY, JW;ZORUMSKI, CF
最近的证据表明，内源性兴奋毒素谷氨酸（Glu）与几种神经系统疾病有关，包括癫痫相关的脑损伤。氯胺酮、苯环利定和MK-801是Glu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kainic酸诱导的行为和/或电痉挛和癫痫相关脑损伤的影响。这些药物减少了行为性癫痫发作的活动，因为电图癫痫发作向新皮层的扩散，但从海马、梨状皮质和杏仁核等脑深部区域记录的癫痫发作并没有明显减少。这三种药物都能预防杏仁核、梨状皮质、丘脑和海马CA1区与癫痫发作相关的脑损伤，但对海马外侧隔区和CA3区几乎没有保护作用。神经保护作用的区域选择性表明，NMDA受体可能在癫痫相关的脑损伤中发挥比其他脑区域更重要的作用。NMDA拮抗剂能够在不抑制癫痫活动的情况下预防几个脑区域的癫痫相关损伤，这表明在这些脑区域，无论是否有NMDA受体的参与，其他递质系统都可以维持持续的癫痫活动，但癫痫相关的脑损伤严重依赖于NMDA受体的参与。
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.