{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:51:00Z","timestamp":1790272260083,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T00:00:00Z","timestamp":1750464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AOD24006\u2010001\u201000000"],"award-info":[{"award-number":["AOD24006\u2010001\u201000000"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>A benzodiazepine (diazepam or midazolam) is one of the current standards of care therapies to effectively terminate organophosphorus nerve agent\u2010induced status epilepticus when administered shortly after onset. Preclinical studies showed that benzodiazepines were less effective in stopping status epilepticus when treatment was delayed up to 30\u2009min from the time of organophosphorus exposure, highlighting the need for adjuncts to midazolam in a delayed treatment scenario. In this study, we evaluated the alpha\u2010amino\u20103\u2010hydroxy\u20105\u2010methylisoxazole\u20104\u2010propionic acid (AMPA) receptor antagonist perampanel for efficacy as a second\u2010line antiseizure medication against soman\u2010induced benzodiazepine\u2010refractory status epilepticus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adult male Sprague\u2013Dawley rats were exposed to a seizure\u2010inducing dose of soman and treated with midazolam (3\u2009mg\/kg; IP) 40\u2009min after seizure onset, followed by perampanel (4\u2009mg\/kg; IP) or vehicle 20\u2009min later. Electroencephalography (EEG) was recorded continuously for 2\u2009weeks for analysis of seizure activity, after which brains were processed for an assessment of neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to midazolam alone, perampanel administered 20\u2009min after midazolam lowered the seizure duration during the first 24\u2009h after soman exposure and reduced the EEG power integral over the 1 and 6\u2009h period following treatment. Rats treated with perampanel as second\u2010line therapy to midazolam had reduced incidence and number of spontaneous recurrent seizures compared to those treated with midazolam alone. The perampanel treatment also reduced neurodegeneration in the fiber tracts, amygdala, and hippocampus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The seizure\u2010protective effects of perampanel as second\u2010line therapy to midazolam provide support for perampanel in treating benzodiazepine\u2010refractory status epilepticus induced by exposure to organophosphorus nerve agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>Treatment of status epilepticus, a life\u2010threatening condition of prolonged seizures, becomes less effective when treatment is delayed. This study used a preclinical rat model of chemical\u2010induced seizure to evaluate the ability of the antiseizure medication perampanel as a second\u2010line therapy to midazolam in the treatment of status epilepticus. We show that perampanel following midazolam treatment improved seizure outcomes and reduced brain damage caused by status epilepticus, compared to midazolam alone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70083","type":"journal-article","created":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T11:29:50Z","timestamp":1750505390000},"page":"1187-1198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Perampanel as a second\u2010line therapy to midazolam reduces soman\u2010induced status epilepticus and neurodegeneration in rats"],"prefix":"10.1002","volume":"10","author":[{"given":"Hailey G.","family":"Steier","sequence":"first","affiliation":[{"name":"Neuroscience Department U.S. Army Medical Research Institute of Chemical Defense (USAMRICD)  Aberdeen Proving Ground Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline 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