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

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.

Analyzing large data sets acquired through telemetry from rats exposed to organophosphorous compounds: an EEG study.

The organophosphorous compound soman is an acetylcholinesterase inhibitor that causes damage to the brain. Exposure to soman causes neuropathology as a result of prolonged and recurrent seizures. In the present study, long-term recordings of cortical EEG were used to develop an unbiased means to quantify measures of seizure activity in a large data set while excluding other signal types. Rats were implanted with telemetry transmitters and exposed to soman followed by treatment with therapeutics similar to those administered in the field after nerve agent exposure. EEG, activity and temperature were recorded continuously for a minimum of 2 days pre-exposure and 15 days post-exposure. A set of automatic MATLAB algorithms have been developed to remove artifacts and measure the characteristics of long-term EEG recordings. The algorithms use short-time Fourier transforms to compute the power spectrum of the signal for 2-s intervals. The spectrum is then divided into the delta, theta, alpha, and beta frequency bands. A linear fit to the power spectrum is used to distinguish normal EEG activity from artifacts and high amplitude spike wave activity. Changes in time spent in seizure over a prolonged period are a powerful indicator of the effects of novel therapeutics against seizures. A graphical user interface has been created that simultaneously plots the raw EEG in the time domain, the power spectrum, and the wavelet transform. Motor activity and temperature are associated with EEG changes. The accuracy of this algorithm is also verified against visual inspection of video recordings up to 3 days after exposure.