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Characterization and treatment of spontaneous recurrent seizures following nerve agent-induced status epilepticus in mice
Journal article   Peer reviewed

Characterization and treatment of spontaneous recurrent seizures following nerve agent-induced status epilepticus in mice

Hilary S McCarren, Margaret R Eisen, Dominique L Nguyen, Parker B Dubée, Cherish E Ardinger, Emily N Dunn, Kari M Haines, Antonia N Santoro, Paige M Bodner, Celinia A Ondeck, …
Epilepsy research, v 162, 106320
01 May 2020
DOI: https://doi.org/10.1016/j.eplepsyres.2020.106320
PMID: 32182542
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.eplepsyres.2020.106320View
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Abstract

Animals Anticonvulsants - therapeutic use Disease Models, Animal Levetiracetam - therapeutic use Mice Nerve Agents - adverse effects Phenobarbital - therapeutic use Soman - adverse effects Status Epilepticus - chemically induced Status Epilepticus - diagnosis Status Epilepticus - drug therapy Status Epilepticus - physiopathology Valproic Acid - therapeutic use
To develop and characterize a mouse model of spontaneous recurrent seizures following nerve agent-induced status epilepticus (SE) and test the efficacy of existing antiepileptic drugs. SE was induced in telemeterized male C57Bl6/J mice by soman exposure, and electroencephalographic activity was recorded for 4-6 weeks. Mice were treated with antiepileptic drugs (levetiracetam, valproic acid, phenobarbital) or corresponding vehicles for 14 d after exposure, followed by 14 d of drug washout. Survival, body weight, seizure characteristics, and histopathology were used to characterize the acute and chronic effects of nerve agent exposure and to evaluate the efficacy of treatments in mitigating or preventing neurological effects. Spontaneous recurrent seizures manifested in all survivors, but the number and frequency of seizures varied considerably among mice. In untreated mice, seizures became longer over time. Moderate to severe histopathology was observed in the amygdala, piriform cortex, and CA1. Levetiracetam provided modest improvements in neurological parameters such as reduced spike rate and improved histopathology scores, whereas valproic acid and phenobarbital were largely ineffective. This model of post-SE spontaneous recurrent seizures differs from other experimental models in the brief latency to seizure development, the occurrence of seizures in 100 % of exposed animals, and the lack of damage to CA4/dentate gyrus. It may serve as a useful tool for rapidly and efficiently screening novel therapies that would be effective against severe epilepsy cases.

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8 citations in Scopus

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Web of Science research areas
Clinical Neurology
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