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Rodent models, widely used to evaluate novel medical countermeasures (MCM<\/jats:styled-content>s) against CWNA<\/jats:styled-content> exposure, normally express plasma carboxylesterase, an enzyme involved in the metabolism of certain organophosphorus compounds. To better predict the efficacy of novel MCM<\/jats:styled-content>s against CWNA<\/jats:styled-content> 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<\/jats:styled-content> exposure with delayed anticonvulsant treatment in the plasma carboxylesterase knockout (ES<\/jats:styled-content>1\u2212\/\u2212) mouse.<\/jats:p><\/jats:sec>Methods<\/jats:title>Electroencephalography (EEG) electrode\u2010implanted ES<\/jats:styled-content>1\u2212\/\u2212 and wild\u2010type (C57BL<\/jats:styled-content>\/6) mice were exposed to various seizure\u2010inducing doses of GD<\/jats:styled-content>, treated with atropine sulfate and the oxime HI<\/jats:styled-content>\u20106 at 1\u00a0minute after exposure, and administered midazolam at 15\u201030\u00a0minutes following the onset of seizure activity. The latency of acute seizure onset and spontaneous recurrent seizures (SRS) was assessed, as were changes in EEG<\/jats:styled-content> power spectra. At 2\u00a0weeks after GD<\/jats:styled-content> exposure, neurodegeneration and neuroinflammation were assessed.<\/jats:p><\/jats:sec>Results<\/jats:title>GD<\/jats:styled-content>\u2010exposed ES<\/jats:styled-content>1\u2212\/\u2212 mice displayed a dose\u2010dependent response in seizure severity. Only ES<\/jats:styled-content>1\u2212\/\u2212 mice exposed to the highest tested dose of GD<\/jats:styled-content> developed SE<\/jats:styled-content>, subchronic alterations in EEG<\/jats:styled-content> power spectra, and SRS<\/jats:styled-content>. Degree of neuronal cell loss and neuroinflammation were dose\u2010dependent; no significant neuropathology was observed in C57BL<\/jats:styled-content>\/6 mice or ES<\/jats:styled-content>1\u2212\/\u2212 mice exposed to lower GD<\/jats:styled-content> doses.<\/jats:p><\/jats:sec>Significance<\/jats:title>The US Food and Drug Administration (FDA)<\/jats:styled-content> animal rule requires the use of relevant animal models for the advancement of MCMs<\/jats:styled-content> against CWNA<\/jats:styled-content>s. We present evidence that argues for the use of the ES<\/jats:styled-content>1\u2212\/\u2212 mouse model to screen anticonvulsant, antiepileptic, and\/or neuroprotective drugs against GD<\/jats:styled-content>\u2010induced toxicity, as well as to identify mechanisms of GD<\/jats:styled-content>\u2010induced epileptogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.14582","type":"journal-article","created":{"date-parts":[[2018,10,28]],"date-time":"2018-10-28T15:17:07Z","timestamp":1540739827000},"page":"2206-2218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Soman\u2010induced status epilepticus, epileptogenesis, and neuropathology in carboxylesterase knockout mice treated with midazolam"],"prefix":"10.1111","volume":"59","author":[{"given":"Brenda","family":"Marrero\u2010Rosado","sequence":"first","affiliation":[{"name":"US Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground 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