Abstracts

Epileptogensis is triggered by diverse factors such as stroke, brain injury or prolonged seizures. Stroke is a major risk factor for development of epilepsy, especially in older populations, and exhibits a strong sex difference. However, the mechanism underlying the post-stroke epilepsy (PSE) remains unclear. There are few validated animal models of PSE in the disease prone females. In this study, we investigated PSE in female rats by using monitoring epileptogenic seizures after stroke induced by middle cerebral artery occlusion (MCAO).

MCAO was induced by intracerebral injection of endothelin-1 in mature adult (MA, 5 months, cyclic) and reproductively senescent (RS, 11 months, acyclic) female rats. Animals were recorded for the occurrence of behavioral and electrographic seizures by a continuous 24/7 video-EEG system for one week at 2, 4, 6, 8, 10 and 12 months. The extent of brain damage was assessed 12 months after MCAO or pilocarpine injections by neuropathology analysis of neurodegeneration and neuronal injury.

Epileptiform seizure discharges were detected in 25% of RS and 40% of MA female rats at 4 months; and in 50% of RS and 33% of MA female rats at 6 month after stroke (p<0.05 vs control; . n=4-13). However, spontaneous seizures were not evident at 8, 10 or 12 months after stoke. Stroke induced epileptogenesis was significantly accelerated after pilocarpine challenge (second hit) wherein all animals showed spontaneous seizure (1-2 seizures/day; p<0.05 vs MCAO control without pilocarpine). After 12 months of MCAO, neuropathology findings showed significant neurodegeneration (20-40% vs control) in NeuN staining in ipsilateral hippocampus of the MCAO group alone and bilaterally in the hippocampus in the group that received pilocarpine 8 weeks post MCAO group (p<0.05 vs. control).