Evaluating an etiologically relevant platform for therapy development for temporal lobe epilepsy: effects of carbamazepine and valproic acid on acute seizures and chronic behavioral comorbidities in the Theiler's murine encephalomyelitis virus mouse model

The Journal of Pharmacology and Experimental Therapeutics
Melissa L Barker-HaliskiH Steve White

Abstract

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 significa...Continue Reading

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Citations

Oct 2, 2015·Acta Neuropathologica·Annamaria VezzaniWolfgang Löscher
Mar 6, 2016·Journal of Neuropathology and Experimental Neurology·Jaycie L LoewenKaren S Wilcox
May 1, 2015·Drugs·Melissa L Barker-HaliskiH Steve White
Aug 4, 2019·The Journal of Pharmacology and Experimental Therapeutics·Stacey MeekerMelissa Barker-Haliski
Jul 29, 2016·Epilepsia·Melissa L Barker-HaliskiH Steve White
Mar 18, 2017·Neurochemical Research·Melissa L Barker-HaliskiKaren S Wilcox
Jul 7, 2018·Molecular Neurobiology·Luca BartoliniWilliam D Gaillard

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