Abstracts

Rationale: The mechanisms of injured brain that establish poststroke seizures and epilepsy are not well understood, largely because animal modeling has had limited development.  This study was undertaken to determine whether animal age, infarction, or their potential interaction could generate poststroke epilepsy within a brief period of time. Methods: Twenty-four (24) male F344 rats (4-months-of- age, n=12; 20-months-of-age, n=12) were divided within each age group for sham-operation (n=6) or lesioning (n=6) by transient (3 h) unilateral MCA/CCAo. All lesioned animals underwent sensorimotor behavioral testing 24 h after surgery as a measure of ischemic injury. Epidural skull screw electrodes were placed in the skulls of animals for video-EEG recordings that began approximately 7 days later and continued intermittently up to a 2-mo post-lesioning time point.  Seizure frequency (number of grade 3, 4, and 5 seizures per hour) was used as the primary outcome measurement for investigating the “age” and “infarction” factor effects on the electrobehavioral evidence of poststroke epilepsy.  A 2 x 2 factorial ANOVA was applied to test the significance of each factor effect as well as the interaction effect between the two factors. In addition, Pearson’s correlation coefficient (r) was calculated to assess the relationship between behavioral scores and lesion volumes in 4- and 20-mo animals. Results: Video-EEG recordings were obtained during 166 recording sessions totaling 3591 h from 17 of 24 (71%) animals up to the 2-mo time point following sham operation or lesioning by MCA/CCAo. Three of 4 (75%) 4-mo MCA/CCAo animals had recurrent episodes of forelimb or hindlimb clonus (grade 3). All 20-mo MCA/CCAo and sham-operated animals demonstrated forelimb clonus, which typically lasted 5-20 sec. Two of 4 (50%) 4-mo MCA/CCAo animals had recurrent episodes of running and rearing (grade 4), whereas all 20-mo MCA/CCAo animals demonstrated these events. 4-mo animals did not demonstrate jumping and falling (grade 5), whereas all 20-mo MCA/CCAo animals did. Interestingly, 2 of 6 (33%) 20-mo sham-operated animals also demonstrated similar episodes of running and falling. 2 x 2 factorial ANOVA revealed that both “age” and “infarction” factors had significant effects on seizure frequency (p = 0.012 and 0.014, respectively); the interaction between the two factors was not significant (p = 0.097). Mean cortical infarct volume in 4-month-old animals was 35.8±10.8 mm3 (range 6.1 to 84.9 mm3, n=6), and in 20-month-old animals was 50.4±18.0 mm3 (range 7.6 to 101.5 mm3, n=5; t-test, p=0.49), indicating no significant difference in infarct volumes between the two age groups. Infarct volume did not demonstrate a direct correlation with behavioral scores for either 4-mo (r=0.5165, p=0.2941) or 20-mo (0.3998, p=0.5049) animals. Conclusions: MCA/CCAo appears to be effective in generating poststroke epilepsy in a relatively brief period of time in both young and aged F344 rats. It remains uncertain as to why 20-month-old sham-operated animals demonstrated grade 3 and 5 seizures in this study but raises the possibility of an age-related propensity to seizure activity in the F344 strain. Funding: Supported by Health Research Formula Fund RFA 01-07-26 from the Pennsylvania Department of Health (Tobacco Settlement Fund), the Targeted Research Initiative for Seniors of the Epilepsy Foundation funded by a grant from the Centers for Disease Control and Prevention, the NIA Animal Allocation Program for Pilot Study Research Support, and NINDS R21NS052722  (KMK).