Aging alters electroencephalographic and clinical manifestations of kainate-induced status epilepticus

Abstract

Purpose: The elderly exhibit an increased risk for developing status epilepticus and status-related morbidity and mortality. However, it is unclear how aging alters the progression of electroencephalographic (EEG) activity and behavioral manifestations during status epilepticus. Methods: A repetitive low-dose kainate treatment protocol (2.5 mg/kg/h; i.p.) was used in this study in conjunction with EEG and behavioral monitoring from freely behaving adult (7-8 months) and aged (22-25 months) Fischer 344 rats to assess the effects of aging on status epilepticus. Results: During kainate treatment, both groups exhibited an increase in EEG power that corresponded with the time course of kainate treatment. However, visual inspection and spectral analysis revealed a reduction of the faster frequencies (12.5-35 Hz) in the EEGs of aged rodents. A similar progression of behavioral manifestations was observed in adult and aged rodents during kainate treatment, although the frequency of preseizure manifestations (e.g., wet-dog shakes; aged rats, 110 events/h vs. adults, 25 events/h; median values) was greater, and latency to onset for any given behavioral manifestation (e.g., class V seizures; aged median, 60 min, vs. adult median, 145 min) was consistently shorter within the aged group. Conclusions: These data reveal that aged Fischer 344 rats exhibit altered EEG activity (reduction of higher frequencies) and clinical manifestations during kainate-induced status epilepticus. Taken together, these data indicate an age-related change in seizure onset and spread after exposure to glutamate analogues.