English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Summary   Objective  Exposure to chemical warfare nerve agents ( CWNA s), 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 ( MCM s) against  CWNA  exposure, normally express plasma carboxylesterase, an enzyme involved in the metabolism of certain organophosphorus compounds. To better predict the efficacy of novel  MCM s 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 ( ES 1−/−) mouse.    Methods  Electroencephalography (EEG) electrode‐implanted  ES 1−/− and wild‐type (C57 BL /6) mice were exposed to various seizure‐inducing doses of  GD , treated with atropine sulfate and the oxime  HI ‐6 at 1 minute after exposure, and administered midazolam at 15‐30 minutes following the onset of seizure activity. The latency of acute seizure onset and spontaneous recurrent seizures (SRS) was assessed, as were changes in  EEG  power spectra. At 2 weeks after  GD  exposure, neurodegeneration and neuroinflammation were assessed.    Results   GD ‐exposed  ES 1−/− mice displayed a dose‐dependent response in seizure severity. Only  ES 1−/− mice exposed to the highest tested dose of  GD  developed  SE , subchronic alterations in  EEG  power spectra, and  SRS . Degree of neuronal cell loss and neuroinflammation were dose‐dependent; no significant neuropathology was observed in C57 BL /6 mice or  ES 1−/− mice exposed to lower  GD  doses.    Significance  The US Food and Drug Administration ( FDA)  animal rule requires the use of relevant animal models for the advancement of  MCMs  against  CWNA s. We present evidence that argues for the use of the  ES 1−/− mouse model to screen anticonvulsant, antiepileptic, and/or neuroprotective drugs against  GD ‐induced toxicity, as well as to identify mechanisms of  GD ‐induced epileptogenesis.

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