Abstracts

Rationale: Temporal lobe epilepsy (TLE) represents a significant portion of acquired epilepsy cases, and is the most common type of pharmacoresistant epilepsy.  Endogenous neurosteroids such as allopregnanolone act as anticonvulsants, and modulation of neurosteroid levels has been shown to affect seizure susceptibility and epileptogenesis. Therefore, we aimed to investigate the effect of inhibiting endogenous neurosteroid synthesis using finasteride, a 5α-reductase inhibitor, on epileptogenesis following pilocarpine-induced status epilepticus (SE), a common and well-characterized model of TLE and limbic epileptogenesis.  Methods: Male C57Bl6 mice, aged 12-14 weeks were used for this study. One-week prior to the study, mice were implanted with wireless telemetry devices (DSI Inc.), providing for 24-hour video-EEG monitoring. SE was induced by the pilocarpine (300 mg/kg, i.p.) paradigm. Diazepam was given to end SE after 2 hours. Continuous 24/7 EEG-video recording was carried out for 90 days following SE, with the finasteride cohort receiving 50 mg/kg (i.p.) for 2 weeks.  Results: In control mice, SRS was noted in 75% with average latency of 7 days. Seizure expression progressed through the 90 days following SE, averaging 49 seizures/animal, with 22s average duration. Finasteride-treated cohorts displayed significantly accelerated and enhanced epileptogenesis. All finasteride-treated animals developed SRS (100%), with an average latency of 3 days. Daily seizure frequency was significantly higher than in control group, with finasteride animals averaging 87 seizures/animal and greater time spent in seizures. However, average seizure duration did not vary between control and finasteride-treated cohorts.   Conclusions: Inhibition of neurosteroid synthesis following SE resulted in acceleration and augmentation of epileptogenesis. These results provide strong evidence supporting the protective role of endogenous neurosteroids in attenuating epileptogenesis following SE.  Funding: **Supported by TAMHSC funds**