7. Convulsive and non-convulsive seizures observed from aging mice following brian ischemia episodes

Abstract

Purpose Stroke is a leading cause of seizures/epilepsy in the aging/aged population, and seizure development after stroke is associated with poorer prognosis. Currently, seizure genesis after stroke is not well understood, and only limited information is available about post-stroke seizures in aging/aged animals. In particular, early-onset seizures that occur within 24 h post stroke remain to be examined in aging/aged animals. We thus attempted to model the early-onset seizures in aging mice. Methods C57 black mice of 16–20 month-old were used. Unilateral hemispheric ischemia was induced by hypoxia-ischemia or middle cerebral artery occlusion (MCAO) models. The animals were under intensive behavioral monitoring and intracranial EEG recordings to detect post-ischemic seizures and then were euthanized for histological assessments of brain injury. Exposure of mouse brain slices to hypoxia-hypoglycemia episodes were used as in vitro model of brain ischemia, and regional population activities were examined via extracellular recordings. Results Vigorous convulsive seizures were observed within 24 h following the hypoxia-ischemia or MCAO episode. These seizures were associated with EEG discharges in the brainstem regions but not in the hippocampal and neocortical areas. Development of these convulsive seizures correlated closely with extensive brain injury and poorer overall outcomes. In addition, non-convulsive seizures, characterized by hippocampal and cortical EEG discharges in the absence of convulsions, were observed following the MCAO episode and prior to the convulsive seizures. When examined in brain slices, seizure-like discharges were observed from the hippocampal CA3 area but not from the brainstem or neocortical area. Conclusions The early-onset seizures result from severe cerebral ischemia and brain injury. Generation of the convulsive seizures may involve deeper sub-cortical structures particularly the brainstem, and the non-convulsive EEG discharges may originate from the hippocampus. Our data may help understanding genesis of post-stroke seizures in the aging/aged population.