Seizure-Induced Brainstem Hypoxia as a Possible Mechanism of Sudden Unexpected Death in Epilepsy

Abstract

Sudden unexpected death in epilepsy (SUDEP) is believed to result from breathing failure during or shortly after a seizure, but the mechanisms behind this respiratory dysfunction remain unknown. A recently discovered period of local tissue hypoxia that occurs during and following a seizure in the brain regions involved in the seizure provides a novel hypothesis for the neurobiological mechanism underlying SUDEP. This thesis used mouse models of seizures and seizure-induced death to explore the hypothesis that SUDEP is the result of seizure-induced hypoxia in brainstem breathing centers. Mice died following generalized, convulsive seizures with epileptiform activity in the brainstem. A brainstem breathing center became severely hypoxic exclusively during and after fatal seizures, following which breathing ceased and the heart stopped beating. These results suggest that seizure-induced hypoxia in brainstem breathing centers is a potential mechanism of the respiratory dysfunction that causes SUDEP and provides a novel target for preventative therapies.