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This possibility could be tested using the peripherally active inhibitor of 3\u03b2\u2010hydroxysteroid dehydrogenase\/\u0394<jats:sup>5\u20104<\/jats:sup> isomerase trilostane, which has been shown repeatedly to increase allopregnanolone levels in the brain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Trilostane (50\u2009mg\/kg) was administered subcutaneously once daily for up to six consecutive days, starting 10\u00a0min after intraperitoneal administration of kainic acid (15\u2009mg\/kg). Seizures were evaluated by video\u2010electrocorticographic recordings for 70\u2009days maximum, and endogenous neurosteroid levels were assessed by liquid chromatography\u2013electrospray tandem mass spectrometry. Immunohistochemical staining was performed to evaluate the presence of brain lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Trilostane did not alter the latency of kainic acid\u2010induced SE onset or its overall duration. When compared to the vehicle\u2010treated group, rats receiving six daily trilostane injections presented a remarkable delay of the first spontaneous electrocorticographic seizure and subsequent tonic\u2013clonic spontaneous recurrent seizures (SRSs). Conversely, rats treated with only the first trilostane injection during SE did not differ from vehicle\u2010treated rats in developing the SRSs. Notably, trilostane did not modify neuronal cell densities or the overall damage in the hippocampus. In comparison to the vehicle group, repeated administration of trilostane significantly decreased the activated microglia morphology in the subiculum. As expected, allopregnanolone and other neurosteroid levels were remarkably increased in the hippocampus and neocortex of rats treated for 6\u2009days with trilostane, but pregnanolone was barely detectable. Neurosteroids returned to basal levels after a week of trilostane washout.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Overall, these results suggest that trilostane led to a remarkable increase in allopregnanolone brain levels, which was associated with protracted effects on epileptogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17561","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T10:47:07Z","timestamp":1677754027000},"page":"1376-1389","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Antiepileptogenic effects of trilostane in the kainic acid model of temporal lobe epilepsy"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3152-9890","authenticated-orcid":false,"given":"Anna Maria","family":"Costa","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic, and Neural Sciences 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