Abstracts

Rationale: Acquired epilepsy is caused by diverse factors such as stroke, brain injury, infections, or prolonged seizures. Stroke is a major risk factor for development of epilepsy, especially in older people, and within this demographic, women develop epilepsy more often than men after stroke. Stroke-induced epilepsy presents unique challenges in the elderly including the quality of life. However, the mechanism underlying the stroke-induced epilepsy remains unclear and there are few validated animal models of post-stroke epilepsy especially in the disease prone group such as the females. In this study, we sought to monitor epileptic seizures in female rats after stroke induced by middle cerebral artery occlusion (MCAO). Methods: MCAO was induced by intracerebral injection of endothelin-1 (600 pmol) in adult (6 months, cyclic) and middle-aged (11 months, acyclic) female rats. Animals were recorded for the occurrence of behavioral and electrographic spontaneous seizures by a continuous 24/7 video-EEG system for one week at 2, 4, 6, 8, 10, and 12 months. Second hit approach of epileptogenesis was obtained by a controlled 2 h status epilepticus induced by lithium-pilocarpine treatment. Results: Epileptiform "seizure-like" discharge were detected in 25% (1 of 6 adults) and 40% (2 of 5 middle-aged) of rats at 4 months; and 50% (1 of 2 adult) and 33.3% (1 of 3 middle-aged) at 6 months after stroke; spontaneous seizures were not evident at 8, 10, or 12 months after stroke. Stroke incited epileptogenesis, however, can be accelerated with pilocarpine administration. The latency for development of epilepsy with spontaneous seizures in adult females was much shorter (~4 days) as compared to middle-aged females (>7 days). Average number of seizure occurrence were analyzed as 0.2 seizures/day in adult and 2.6 seizures/day in middle-aged female rats in stroke+pilocarpine group. Both adult and middle-aged females showed approximately 0.5 seizures per day in control (non-stroke) pilocarpine group. Conclusions: Overall, these results indicate that MCAO-induced stroke is a potential epileptogenic trigger with extremely low incidence, but this condition is sensitive to a second brain injury. Funding: Supported by TAMHSC WHIN program.