Abstracts

Middle cerebral artery occlusion (MCAO) is a well-established model of stroke, yet no study using MCAO has demonstrated the development of poststroke epilepsy. We assessed the MCAO model for its potential to generate epileptogenesis by testing both young adult and aged rats to determine whether age was a critical variable. Six 2.5 mo old Long Evans rats were lesioned by transient (3 hour) unilateral occlusion of the left middle cerebral and common carotid arteries (MCA/CCAO), and five animals were sham-operated. Animals were implanted with six skull screw electrodes, and were entered into a rotating weekly schedule of video-EEG monitoring for 6 months following lesioning. Additionally, four 4 mo old and five 20 mo old Fischer 344 rats were subjected to the same procedures. Our initial study using young adult Long Evans animals showed similarities, but also significant differences between lesioned and control EEG recordings. Both cohorts demonstrated brief, focal, 1-3 sec 7-Hz spike-wave discharges originating independently or synchronously from bilateral hemispheres without any observable change in normal behavior. More prolonged, generalized 7-Hz spike-wave discharges with prominent motor arrest were frequent in all five control animals (100%), but present in only two (33%) of the six lesioned animals. These discharges in lesioned animals were shorter in duration and decreased in frequency of occurrence compared to those of the control group. However, no lesion-associated epileptic seizure was recorded during the six-month monitoring period. Preliminary studies of four 4 mo old F344 lesioned animals have not demonstrated any evidence of convulsive seizure activity. In contrast, 5/5 (100%) 20 mo old animals have demonstrated spontaneous, recurrent convulsive seizures within the first month following lesioning. Seizures were characterized by ictal EEG patterns associated with Racine grade 4-5 convulsions. Interictal EEG records and animal behavior was otherwise normal. These results indicate the ability of transient unilateral MCA/CCAO to generate poststroke epilepsy characterized by recurrent convulsive seizures when used in aged animals. These findings suggest a physiologically relevant animal model of poststroke epilepsy in the elderly and establish the groundwork for a working model of poststroke epileptogenesis so that translational studies can shift from the control of symptoms to potential prevention and cure. (Supported by an NIH-NIA pilot study award, and Pennsylvania Department of Health RFA 01-07-26 awarded to KMK.)