BAD knockout provides metabolic seizure resistance in a genetic model of epilepsy with sudden unexplained death in epilepsy.

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 BadKO provides seizure resistance in a genetic model of chronic epilepsy.