谷歌浏览器插件
订阅小程序
在清言上使用

Ketamine as adjunct to midazolam treatment following soman-induced status epilepticus reduces seizure severity, epileptogenesis, and brain pathology in plasma carboxylesterase knockout mice

Brenda M. Marrero-Rosado, Marcio de Araujo Furtado, Erica R. Kundrick, Katie A. Walker, Michael F. Stone, Caroline R. Schultz, Donna A. Nguyen, Lucille A. Lumley

Epilepsy & behavior(2020)

引用 13|浏览8
暂无评分
摘要
Delayed treatment of cholinergic seizure results in benzodiazepine-refractory status epilepticus (SE) that is thought, at least in part, to result from maladaptive trafficking of N-methyl-D-aspartate (NMDA) and gammaaminobutyric acid type A (GABA(A)) receptors, the effects of which may be ameliorated by combination therapy with the NMDA receptor antagonist ketamine. Our objective was to establish whether ketamine and midazolam dual therapy would improve outcome over midazolam monotherapy following soman (GD) exposure when evaluated in a mouse model that, similar to humans, lacks plasma carboxylesterase, greatly reducing endogenous scavenging of GD. In the current study, continuous cortical electroencephalographic activity was evaluated in male and female plasma carboxylesterase knockout mice exposed to a seizure-inducing dose of GD and treated with midazolam or with midazolam and ketamine combination at 40 min after seizure onset. Ketamine and midazolam combination reduced GD-induced lethality, seizure severity, and the number of mice that developed spontaneous recurrent seizure (SRS) compared with midazolam monotherapy. In addition, ketamine-midazolam combination treatment reduced GD-induced neuronal degeneration and microgliosis. These results support that combination of antiepileptic drug therapies aimed at correcting the maladaptive GABA(A) and NMDA receptor trafficking reduces the detrimental effects of GD exposure. Ketamine may be a beneficial adjunct to midazolam in reducing the epileptogenesis and neuroanatomical damage that follows nerve agent exposure and pharmacoresistant SE. Published by Elsevier Inc.
更多
查看译文
关键词
Ketamine,Neuroinflammation,Spontaneous recurrent seizure,Organophosphorus,Benzodiazepine-resistant status epilepticus,Antiepileptic
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要