{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T12:58:08Z","timestamp":1781787488328,"version":"3.54.5"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T00:00:00Z","timestamp":1705708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Trilostane is a 3\u03b2\u2010hydroxysteroid dehydrogenase\/\u0394<jats:sup>5\u20104<\/jats:sup> isomerase inhibitor able to produce a manyfold increase in brain levels of various neurosteroids, including allopregnanolone. We previously found that treatment with trilostane can slow down epileptogenesis in the kainic acid (KA) model of temporal lobe epilepsy. It is unknown whether trilostane may have a similar effect on the progression of epilepsy severity, as observed in KA\u2010treated rats. Consequently, we investigated the effects of trilostane (50\u2009mg\/kg\/day, 1 week) in epileptic rats, given 64\u2009days after KA administration. Seizures were monitored by video\u2010electrocorticographic recordings before and during the treatment with trilostane or vehicle (sesame oil), and neurosteroid levels were measured in serum and cerebral tissue using liquid chromatography\u2013electrospray tandem mass spectrometry after treatment. Pregnenolone sulfate, pregnenolone, progesterone, 5\u03b1\u2010dihydroprogesterone, and allopregnanolone peripheral levels were massively increased by trilostane. With the only exception of hippocampal pregnenolone sulfate, the other neurosteroids augmented in both the neocortex and hippocampus. Only pregnanolone levels were not upregulated by trilostane. As expected, a significant increase in the seizure occurrence was observed in rats receiving the vehicle, but not in the trilostane group. This suggests that the increased availability of neurosteroids produced a disease\u2010modifying effect in the brain of epileptic rats.<\/jats:p>","DOI":"10.1111\/epi.17887","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T09:45:05Z","timestamp":1705743905000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Seizure progression is slowed by enhancing neurosteroid availability in the brain of epileptic rats"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5189-1008","authenticated-orcid":false,"given":"Mohammad","family":"Gol","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic, and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3152-9890","authenticated-orcid":false,"given":"Anna Maria","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic, and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7130-2511","authenticated-orcid":false,"given":"Giuseppe","family":"Biagini","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic, and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"},{"name":"Center for Neuroscience and Neurotechnology University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0965-2948","authenticated-orcid":false,"given":"Chiara","family":"Lucchi","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic, and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12526"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16955"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.33594\/000000232"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0980-08.2009"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2015.08.016"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17561"},{"key":"e_1_2_9_8_1","article-title":"Neurosteroids and focal epileptic disorders","volume":"10","author":"L\u00e9vesque M","year":"2020","journal-title":"Int J Mol Sci"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000509093"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16654"},{"key":"e_1_2_9_11_1","first-page":"397","article-title":"Update on the use of trilostane in dogs","volume":"59","author":"Lemetayer J","year":"2018","journal-title":"Can Vet J"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.09.005"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2013.10.011"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0337-20.2021"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031198"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024966"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2019.100788"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9092091"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12040963"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T16:46:56Z","timestamp":1747673216000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.17887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,20]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/epi.17887"],"URL":"https:\/\/doi.org\/10.1111\/epi.17887","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,20]]},"assertion":[{"value":"2023-10-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}