Abstracts

Rationale: The pathophysiological mechanisms of epileptogenesis following ischemic stroke in the aged brain are not well understood, yet poststroke epilepsy among elderly populations is clinically prevalent. This lack of mechanistic understanding can be attributed to limited developments in animal modeling of poststroke epilepsy.Methods: We utilized permanent and transient (3 h) unilateral middle cerebral artery (MCA) and common carotid artery (CCA) occlusion (MCA/CCAo) coupled with video-only and/or video-EEG monitoring after implantation of cortical and hippocampal depth electrodes as a means for assessing EEG and behavioral changes associated with poststroke epileptogenesis in 4, 12 and 20 mo. old Fischer 344 (F344) rats. We hypothesized that advancing age and reperfusion injury following transient occlusion would result in increased seizure frequencies compared to younger animals subjected to permanent MCA/CCAo.Results: A total of 35 lesioned animals comprising six experimental categories underwent 17836.9 hours of monitoring. Nine of these animals (26%) underwent video-EEG monitoring. The average period between lesioning and electrode implantation was 256.9 20.3 days. This delay was attributed to high premature mortality rates following MCA/CCAo. Animals appeared to have a greater likelihood of surviving electrode implantation after prolonged postoperative recovery periods consisting of video-only monitoring. No EEG recordings were obtained from 12 mo. old transient occlusion and 20 mo. old transient and permanent occlusion animals due to premature deaths. Five animals (14%) demonstrated seizure activity after MCA/CCAo: three 12 mo. old permanent occlusion animals, one 4 mo. old permanent occlusion animal and one 4 mo. old transient occlusion animal. The average period between lesioning and first recorded seizures was 316.6 22.3 days (range 257 385 days). Of these five animals, three demonstrated behavioral seizures (Class 3-5) accompanied by generalized ictal EEG activity. Three of the five animals demonstrated 1-2 Hz spike-and-wave discharges (SWDs) associated with motor arrest. One animal s discharges were generalized across all four EEG channels, while the other two animals SWDs were confined to the left (ipsilateral to lesion) frontal cortical channel. Gross inspection of brains revealed variability in lesion presence and size among age groups and occlusion types. Estimation of infarct volume was inexact due to variation in survival times. Timm staining revealed no evidence of mossy fiber sprouting in any animal.Conclusions: This study provides a limited description of electrobehavioral properties of young adult, mid-aged, and aged F344 rats after MCA/CCAo, detailing evidence of focal nonconvulsive electrographic SWDs and behavioral seizures in both permanent and transient occlusion animals of differing ages. These findings indicate that MCA/CCAo can be a viable method for modeling poststroke epilepsy. Further investigation, specifically larger age group/occlusion type cohorts and a more complete sampling of video-EEG recordings from these groups, is necessary to validate these suggestions.