4.5 Article

Spontaneous recurrent seizures after status epilepticus induced by soman in Sprague-Dawley rats

Journal

EPILEPSIA
Volume 51, Issue 8, Pages 1503-1510

Publisher

WILEY
DOI: 10.1111/j.1528-1167.2009.02478.x

Keywords

Organophosphorus; Status epilepticus; EEG; Neuropathology; Spontaneous recurrent seizures

Funding

  1. Defense Threat Reduction Agency [I.E0042-08-WR-C]

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P>Purpose: Exposure to toxic levels of organophosphorus (OP) nerve agents can lead to seizures, respiratory failure, and, if untreated, death. The cholinesterase inhibitor soman belongs to the class of OP nerve agents and can cause status epilepticus (SE) and brain damage due to neuroexcitotoxicity. In the present study, electroencephalographic seizures are characterized through telemetry implants in rats exposed to soman, followed by treatment with therapeutics similar to those administered after nerve agent exposure. Methods: Cortical electroencephalography (EEG), motor activity and body temperature were recorded continuously for 2 days preexposure and 15 days postexposure to verify the occurrence of spontaneous recurrent seizures (SRS) after soman exposure. Results: Behavioral seizures were monitored and the latency to SE was 7.8 +/- 4.0 min after exposure. Among the rats that showed SE, approximately 90% had prolonged seizures within the initial 3 days after soman exposure. Five percent of the rats developed stage 1 seizures, 16% stage 2, 23% stage 3, 18% stage 4, and 38% stage 5. Seventy-nine percent of the rats presented SE and epileptiform-like discharges several days after SE, and 28.9% of those with SE experienced electrographic SRS. The latency to the appearance of SRS ranged from 5-10 days. Fiber degeneration evaluated through silver staining revealed damage in cortical and subcortical areas directly correlated with SE. Discussion: The presence of SRS after seizures induced by soman highlights the importance of quantifying SRS in studies where the objective is to find new therapeutics against soman-induced seizures.

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