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Animals receiving DFP followed by atropine and pralidoxime exhibited continuous high\u2010amplitude rhythmical electroencephalography (EEG) spike activity and behavioral seizures for more than 5\u00a0hours. Treatments were administered intramuscularly 40\u00a0min after DFP. Seizures persisted following midazolam (1.8 mg\/kg). The combination of midazolam with either allopregnanolone (6 mg\/kg) or perampanel (2 mg\/kg) terminated EEG and behavioral status epilepticus, but the onset of the perampanel effect was slow. The combination of midazolam, allopregnanolone, and perampanel caused rapid and complete suppression of EEG and behavioral seizures. In the absence of DFP, animals treated with the three\u2010drug combination were sedated but not anesthetized. Animals that received midazolam alone exhibited spontaneous recurrent EEG seizures, whereas those that received the three\u2010drug combination did not, demonstrating antiepileptogenic activity. All combination treatments reduced neurodegeneration as assessed with Fluoro\u2010Jade C staining to a greater extent than midazolam alone, and most reduced astrogliosis as assessed by GFAP immunoreactivity but had mixed effects on markers of microglial activation. We conclude that allopregnanolone, a positive modulator of the GABA<jats:sub>A<\/jats:sub> receptor, and perampanel, an AMPA receptor antagonist, are potential adjuncts to midazolam in the treatment of benzodiazepine\u2010refractory organophosphate nerve agent\u2013induced status epilepticus.<\/jats:p>","DOI":"10.1111\/nyas.14479","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T07:30:52Z","timestamp":1600327852000},"page":"183-206","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Allopregnanolone and perampanel as adjuncts to midazolam for treating diisopropylfluorophosphate\u2010induced status epilepticus in rats"],"prefix":"10.1111","volume":"1480","author":[{"given":"Ashish","family":"Dhir","sequence":"first","affiliation":[{"name":"Department of Neurology, School of Medicine University of California, Davis  Sacramento California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald A.","family":"Bruun","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine University of California, Davis  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Guignet","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine University of California, Davis  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Hua","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine University of California, Davis  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine University of California, Davis  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Calsbeek","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine University of California, Davis  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine University of California, Davis  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, School of Medicine University of California, Davis  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Tancredi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine University of California, Davis  Sacramento California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle J.","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, School of Medicine University of California, Davis  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7665-7584","authenticated-orcid":false,"given":"Pamela J.","family":"Lein","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine University of California, Davis  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3296-8193","authenticated-orcid":false,"given":"Michael A.","family":"Rogawski","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine University of California, Davis  Sacramento California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2007.07.004"},{"key":"e_1_2_8_3_1","first-page":"676358","article-title":"New onset refractory status epilepticus as an unusual presentation of a suspected organophosphate poisoning","volume":"2014","author":"Waheed S.","year":"2014","journal-title":"Case Rep. 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