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Rapid control of seizure activity is important to minimize neuronal injury and the resulting neurological and behavioral disorders; however, early treatment will not be possible after mass release of <jats:styled-content style=\"fixed-case\">OP<\/jats:styled-content>s or <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We utilized a delayed\u2010treatment model of <jats:styled-content style=\"fixed-case\">OP<\/jats:styled-content> exposure in adult rats by administration of diisopropyl fluorophosphate (<jats:styled-content style=\"fixed-case\">DFP<\/jats:styled-content>) to study the relationship between the antiseizure and neuroprotective effects of the \u201cstandard\u2010of\u2010care\u201d benzodiazepine, midazolam (<jats:styled-content style=\"fixed-case\">MDZ<\/jats:styled-content>), when given at 30, 60, and 120\u00a0minutes after <jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content> onset. After electroencephalography (<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>) recordings, neural damage in serial brain sections was studied with Fluoro\u2010Jade B staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">MDZ<\/jats:styled-content>\u2010induced seizure suppression was equivalent in magnitude regardless of treatment delay (ie, seizure duration). When assessed globally (ie, normalized across 10 different brain regions) for <jats:italic>each<\/jats:italic> treatment delay, <jats:styled-content style=\"fixed-case\">MDZ<\/jats:styled-content> administration resulted in only nonsignificant reductions in neuronal death. However, when data for <jats:styled-content style=\"fixed-case\">MDZ<\/jats:styled-content> treatment were <jats:italic>combined<\/jats:italic> from all three delay times, a small but significant reduction in global neuronal death was detected when compared to vehicle treatment, which indicated that the substantive <jats:styled-content style=\"fixed-case\">MDZ<\/jats:styled-content>\u2010induced seizure suppression led to only a small reduction in neuronal death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>In conclusion, <jats:styled-content style=\"fixed-case\">MDZ<\/jats:styled-content> significantly reduced <jats:styled-content style=\"fixed-case\">DFP<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content> intensity when treatment was delayed 30, 60, and even up to 120\u00a0minutes; however, this reduction in seizure intensity had no detectable effect on neuronal death at each individual delay time. These data show that although <jats:styled-content style=\"fixed-case\">MDZ<\/jats:styled-content> suppressed seizures, additional neuroprotective therapies are needed to mitigate the effects of <jats:styled-content style=\"fixed-case\">OP<\/jats:styled-content> exposure.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16050","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T16:23:44Z","timestamp":1558715024000},"page":"1387-1398","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Antiseizure and neuroprotective effects of delayed treatment with midazolam in a rodent model of organophosphate exposure"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3968-0608","authenticated-orcid":false,"given":"Jay","family":"Spampanato","sequence":"first","affiliation":[{"name":"Department of Neurosurgery University of Utah School of Medicine Salt Lake City, 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