Scope and contribution of genetic models to an understanding of the epilepsies.
Scope and contribution of genetic models to an understanding of the epilepsies.
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发表时间：
1991
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通讯作者：
P. Jobe;P. K. Mishra;N. Ludvig;J. Dailey
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作者：
P. Jobe;P. K. Mishra;N. Ludvig;J. Dailey
对癫痫遗传模型的研究强调，一些癫痫发作障碍是由异常的“接线图”和个别神经元的异常活动引起的。这些缺陷导致在癫痫神经系统内工作的独特的镇静剂触发机制，但在正常受试者中不活跃或不存在。此外，癫痫的原因不仅存在于最初出现癫痫样脑电放电的大脑区域内，而且还存在于该区域之外。在跨物种的遗传模型中，病因上显著的神经化学功能障碍可能是癫痫状态的共同特征。因此，基因决定的惊厥性癫痫的发生可能部分是由去甲肾上腺素和GABA能缺陷引起的。相反，大鼠以及人类的遗传性失神发作可能是对GABA能过量的反应。遗传性癫痫动物的独特特征强调了它们在开发选择性改善癫痫易感性的新药方面的有用性。
Studies of the genetic models of the epilepsies emphasize that some seizure disorders result from an aberrant "wiring diagram" coupled with abnormal activity of individual neurons. These defects cause the unique seizer-triggering mechanisms operative within the epileptic nervous system but which are inactive or do not exist in normal subjects. Moreover, causes of epilepsy reside not only within the brain area, wherein initial appearance of epileptic EEG discharge occurs, but also outside that region. Etiologically significant neurochemical dysfunctions may be common features of the epileptic condition in genetic models across species. Accordingly, genetically determined convulsive epileptogenesis in rats, baboons, and humans may result partially from noradrenergic and GABAergic deficits. In contrast, genetically derived absence seizures in the rat and perhaps also humans may occur in response to GABAergic excess. The unique features of the genetically epileptic animals emphasize their usefulness in developing novel drugs that selectively ameliorate seizure predisposition.