Modeling early-onset post-ischemic seizures in aging mice

•Aging mice exhibited convulsive seizures (CS) within a few hours following MCAO.•CS occurrence was not preceded or coincided with hippocampal-cortical EEG discharges.•CS development was associated closely with severe brain injury and acute mortality.•Adult mice showed similar CS but better survival following anticonvulsive treatment.

Stroke is the leading cause of seizures and epilepsy in the aged population, with post-stroke seizures being a poor prognostic factor. The pathological processes underlying post-stroke seizures are not well understood and studies of these seizures in aging/aged animals remain scarce. Therefore, our primary objective was to model post-stroke seizures in aging mice (C57 black strain, 16-20 months-old), with a focus on early-onset, convulsive seizures that occur within 24-hours of brain ischemia. We utilized a middle cerebral artery occlusion model and examined seizure activity and brain injury using combined behavioral and electroencephalographic monitoring and histological assessments. Aging mice exhibited vigorous convulsive seizures within hours of the middle cerebral artery occlusion. These seizures manifested with jumping, rapid running, barrel-rolling and/or falling all in the absence of hippocampal-cortical electrographic discharges. Seizure development was closely associated with severe brain injury and acute mortality. Anticonvulsive treatments after seizure occurrence offered temporary seizure control but failed to improve animal survival. A separate cohort of adult mice (6-8 months-old) exhibited analogous early-onset convulsive seizures following the middle cerebral artery occlusion but had better survival outcomes following anticonvulsive treatment. Collectively, our data suggest that early-onset convulsive seizures are a result of severe brain ischemia in aging animals.

Graphical abstractA, aging mice are susceptible to development of convulsive seizures (CS) following MCAO.B, these CS occur largely within a few hours post ischemia.C, non-convulsive seizures (NCS), but not CS, are associated with hippocampal-cortical EEG discharges.Download high-res image (147KB)Download full-size image