Persistently Elevated Gamma Power and Delayed Brain Damage in Aged Rats Acutely Exposed to Soman Without Status Epilepticus: Comparisons with Seizing Rats Treated with Midazolam or with Tezampanel and Caramiphen

Aged animals or humans are more susceptible to permanent brain damage from status epilepticus (SE), making the selection of antiseizure medication even more crucial. This study compared the antiseizure and neuroprotective efficacy of midazolam with that of tezampanel combined with caramiphen in treating soman-induced SE in aged rats. A substantial proportion of soman-exposed aged rats did not develop SE, allowing us to also study this noSE group. SE duration within 24 h post-exposure was significantly longer in the midazolam than the tezampanel + caramiphen group, which was reflected in the EEG power integral. Spectral density analysis showed sustained increase in gamma-band power in the noSE group. Increased delta power in the SE groups lasted longer after midazolam. Body temperature decreased substantially only in the noSE and tezampanel + caramiphen groups. The midazolam group displayed severe neuropathology in the hippocampus and the amygdala 7 days to 6 months post-exposure, whereas the noSE and tezampanel + caramiphen groups exhibited only delayed amygdala damage. Thus, tezampanel + caramiphen has far superior neuroprotective efficacy than midazolam in aged rats. Increased gamma power is associated with seizure resistance; however, even in the absence of SE, delayed neuropathology can develop after a single acute organophosphate exposure.