Oxygenation prevents sudden death in seizure-prone mice

Purpose: Sudden unexpected death in epilepsy (SUDEP) is a significant health problem for some with epilepsy, but no preventive therapy has been developed for high-risk patients. Sudden death in mice, after sound-induced (audiogenic) seizures, can model the seizure-associated respiratory arrest that contributes to SUDEP in some humans and may be useful for evaluating potential SUDEP therapies. This Study evaluated the effects of oxygenation on sudden fatal audiogenic seizures (AGSs) in three mouse strains, DBA/2J (D2), B6SAS, and primed C57BL/6J (B6) that differ in genetic background and seizure etiology (idiopathic or acquired). Methods: The incidence of fatal AGSs was measured in (a) a normal air environment; (b), an oxygen-rich environment; (c) a normal air environment 24 h after a nonfatal AGS; (d) an oxygen-rich environment 24 h after a nonfatal AGS; and (e) a normal air environment 60 s after exposure to an oxygen-rich environment. Results: Sudden, fatal AGS occurred in 100%, 100%, and 58% of the D2, B6SAS, and primed-B6 mice, respectively, in the air environment. Oxygenation completely prevented fatal AGSs in each strain, but had no effect on seizure incidence or severity. Furthermore, the protective effect of oxygenation against fatal seizures occurred only when the mice were in an oxygen-rich environment. Conclusions: These findings indicate that oxygenation prevents sudden death in seizure-prone mice and suggest that oxygenation may protect some seizure-prone humans at risk for SUDEP.