Central nervous system infections can underlie the development of
epilepsy, and Theiler's murine encephalomyelitis virus (TMEV)
infection in C57BL/6J mice provides a novel model of
infection-induced
epilepsy. Approximately 50-65% of infected mice develop acute, handling-induced
seizures during the
infection. Brains display acute neuropathology, and a high number of mice develop spontaneous, recurrent
seizures and behavioral comorbidities weeks later. This study characterized the utility of this model for
drug testing by assessing whether antiseizure
drug treatment during the acute
infection period attenuates handling-induced
seizures, and whether such treatment modifies associated comorbidities. Male C57BL/6J mice infected with TMEV received twice-daily
valproic acid (VPA; 200 mg/kg),
carbamazepine (CBZ; 20 mg/kg), or vehicle during the
infection (days 0-7). Mice were assessed twice daily during the
infection period for handling-induced
seizures. Relative to vehicle-treated mice, more CBZ-treated mice presented with acute
seizures; VPA conferred no change. In mice displaying
seizures, VPA, but not CBZ, reduced seizure burden. Animals were then randomly assigned to acute and long-term follow-up. VPA was associated with significant elevations in acute (day 8)
glial fibrillary acidic protein (astrocytes) immunoreactivity, but did not affect NeuN (neurons) immunoreactivity. Additionally, VPA-treated mice showed improved motor performance 15 days postinfection (DPI). At 36 DPI, CBZ-treated mice traveled significantly less distance through the center of an open field, indicative of anxiety-like behavior. CBZ-treated mice also presented with significant
astrogliosis 36 DPI. Neither CBZ nor VPA prevented long-term reductions in NeuN immunoreactivity. The TMEV model thus provides an etiologically relevant platform to evaluate potential treatments for acute
seizures and disease modification.