期刊
NEUROTOXICOLOGY
卷 82, 期 -, 页码 130-136出版社
ELSEVIER
DOI: 10.1016/j.neuro.2020.12.002
关键词
Chemical warfare nerve agent; Status epilepticus; Anti-seizure; Survival; Cannabinoids
资金
- NIH/NIAID [AOD16024-001-00000]
- USAMRICD [AOD16024-001-00000]
- U.S. Department of Energy
- U.S. Army Medical Research and Development Command
Cannabidiol shows positive effects in a severe seizure model induced by soman, improving survival rate and reducing body weight loss. Additionally, it may enhance the anti-seizure effects of the benzodiazepine midazolam.
Cannabidiol, approved for treatment of pediatric refractory epilepsy, has anti-seizure effects in various animal seizure models. Chemical warfare nerve agents, including soman, are organophosphorus chemicals that can induce seizure and death if untreated or if treatment is delayed. Our objective was to evaluate whether cannabidiol would ameliorate soman-induced toxicity using a mouse model that similar to humans lacks plasma carboxylesterase. In the present study, adult female plasma carboxylesterase knockout (Es1(-/-)) mice were pretreated with cannabidiol (20-150 mg/kg) or vehicle 1 h prior to exposure to a seizure-inducing dose of soman and evaluated for survival and seizure activity. The muscarinic antagonist atropine sulfate and the oxime HI-6 were administered at 1 min after exposure, and the benzodiazepine midazolam was administered at 30 min after seizure onset. Cannabidiol (150 mg/kg) pre-treatment led to a robust increase in survival rate and attenuated body weight loss in soman-exposed mice treated with medical countermeasures, compared to mice pretreated with vehicle. In addition, mice pretreated with cannabidiol (150 mg/kg) had a modest reduction in seizure severity after midazolam treatment compared to vehicle-pretreated. These findings of improved outcome with cannabidiol administration in a severe seizure model of soman exposure provide additional pre-clinical support for the benefits of cannabidiol against exposure to seizure-inducing chemical agents and suggest cannabidiol may augment the anti-seizure effects of midazolam.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据