Spreading depolarization in the brainstem mediates sudden cardiorespiratory arrest in mouse SUDEP models.

ABSTRACT: Cardiorespiratory collapse after a seizure is the leading cause of sudden unexpected death in epilepsy (SUDEP) in young persons, but why only certain individuals are at risk is unknown. To identify a mechanism for this lethal cardiorespiratory failure, we examined whether genes linked to increased SUDEP risk lower the threshold for spreading depolarization (SD), a self-propagating depolarizing wave that silences neuronal networks. Mice carrying mutations in Kv1.1 potassium channels (-/-) and Scn1a sodium ion channels (+/R1407X) phenocopy many aspects of human SUDEP. In mutant, but not wild-type mice, seizures initiated by topical application of 4-aminopyridine to the cortex led to a slow, negative DC potential shift recorded in the dorsal medulla, a brainstem region that controls cardiores

SUBMITTER: Aiba I 

PROVIDER: S-EPMC4852131 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature