Soman‐induced status epilepticus, epileptogenesis, and neuropathology in carboxylesterase knockout mice treated with midazolam

Abstract

Exposure to chemical warfare nerve agents (CWNAs), such as soman (GD), can induce status epilepticus (SE) that becomes refractory to benzodiazepines when treatment is delayed, leading to increased risk of epileptogenesis, severe neuropathology, and long‐term behavioral and cognitive deficits. Rodent models, widely used to evaluate novel medical countermeasures (MCMs) against CWNA exposure, normally express plasma carboxylesterase, an enzyme involved in the metabolism of certain organophosphorus compounds. To better predict the efficacy of novel MCMs against CWNA exposure in human casualties, it is crucial to use appropriate animal models that mirror the human condition. We present a comprehensive characterization of the seizurogenic, epileptogenic, and neuropathologic effects of GD exposure with delayed anticonvulsant treatment in the plasma carboxylesterase knockout (ES1−/−) mouse.

Document Details

Document Type
Pub Defense Publication
Publication Date
Oct 25, 2018
Source ID
10.1111/epi.14582

Entities

People

  • Brenda Marrero‐rosado
  • Caroline R. Schultz
  • Erica Kundrick
  • Fu Du
  • Katie Walker
  • Lucille A. Lumley
  • Marcio De Araujo Furtado
  • Michael Stone
  • Sean O'brien

Organizations

  • Defense Threat Reduction Agency
  • National Institute of Neurological Disorders and Stroke
  • United States Army Medical Research Institute of Chemical Defense

Tags

Fields of Study

  • Biology

Readers

  • Neurotoxicology
  • Neurotrauma and Rehabilitation Medicine.