Seizure progression is slowed by enhancing neurosteroid availability in the brain of epileptic rats

• DOI: 10.1111/epi.17887
• Publication Date: 2024-01-20T09:45:05Z
• Authors: Mohammad Gol; Anna Maria Costa; Giuseppe Biagini; Chiara Lucchi
• Keywords: Allopregnanolone; Pregnenolone sulfate; Pregnanolone

Abstract Trilostane is a 3β‐hydroxysteroid dehydrogenase/Δ 5‐4 isomerase inhibitor able to produce manyfold increase in brain levels of various neurosteroids, including allopregnanolone. We previously found that treatment with trilostane can slow down epileptogenesis the kainic acid (KA) model temporal lobe epilepsy. It unknown whether may have similar effect on progression epilepsy severity, as observed KA‐treated rats. Consequently, we investigated effects (50 mg/kg/day, 1 week) epileptic rats, given 64 days after KA administration. Seizures were monitored by video‐electrocorticographic recordings before and during or vehicle (sesame oil), neurosteroid measured serum cerebral tissue using liquid chromatography–electrospray tandem mass spectrometry treatment. Pregnenolone sulfate, pregnenolone, progesterone, 5α‐dihydroprogesterone, allopregnanolone peripheral massively increased trilostane. With only exception hippocampal pregnenolone other neurosteroids augmented both neocortex hippocampus. Only pregnanolone not upregulated As expected, significant seizure occurrence was rats receiving vehicle, but group. This suggests availability produced disease‐modifying