DBA/1 mice exhibit chronic susceptibility to audiogenic seizures followed by sudden death associated with respiratory arrest

One proposed cause of sudden unexpected death in epilepsy (SUDEP) in patients is generalized convulsive seizures with respiratory malfunction. We evaluated DBA/1 mice as a chronic SUDEP model. In DBA/1 mice, audiogenic seizures induced by acoustic stimulation resulted in generalized convulsive seizures followed by respiratory arrest from postnatal day (PND) 21 to 100. The incidence of respiratory arrest susceptibility increased, reaching similar to 90-100% by three to seven daily seizures when testing began on PND 21-30. Respiratory arrest was reversible with resuscitation in similar to 98% of mice, which allows repeated seizure testing. Electrocardiographic activity in DBA/1 mice was detectable for similar to 4-6 minutes after respiratory arrest, indicating that death is likely due to respiratory cessation, as cardiac changes occur later. These findings suggest that DBA/1 mice are a useful chronic SUDEP model. These mice die suddenly from respiratory arrest after generalized convulsive seizures until reaching PND >= 100, allowing testing of chronic preventive treatments for SUDEP. (C) 2010 Elsevier Inc. All rights reserved.