<scp>BAD</scp> knockout provides metabolic seizure resistance in a genetic model of epilepsy with sudden unexplained death in epilepsy

Abstract

Summary Metabolic alteration, either through the ketogenic diet ( KD ) or by genetic alteration of the BAD protein, can produce seizure protection in acute chemoconvulsant models of epilepsy. To assess the seizure‐protective role of knocking out ( KO ) the Bad gene in a chronic epilepsy model, we used the Kcna1 −/− model of epilepsy, which displays progressively increased seizure severity and recapitulates the early death seen in sudden unexplained death in epilepsy ( SUDEP ). Beginning on postnatal day 24 (P24), we continuously video monitored Kcna1 −/− and Kcna1 −/− Bad −/− double knockout mice to assess survival and seizure severity. We found that Kcna1 −/− Bad −/− mice outlived Kcna1 −/− mice by approximately 2 weeks. Kcna1 −/− Bad −/− mice also spent significantly less time in seizure than Kcna1 −/− mice on P24 and the day of death, showing that Bad KO provides seizure resistance in a genetic model of chronic epilepsy.