{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T21:45:28Z","timestamp":1779399928638,"version":"3.53.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Status epilepticus causes the most severe condition related to epilepsy in terms of high mortality rate. Although status epilepticus treatment guidelines specify a treatment process based on three\u2010stage monotherapy, effective control cannot yet be achieved in all cases. In the presented study, with electrophysiological and behavioral tests, it was aimed to investigate the effectiveness of the combination of midazolam (MDZ), one of the most commonly used benzodiazepines in the first\u2010line treatment of status epilepticus, with the second\u2010line antiepileptics levetiracetam (LEV), lacosamide (LCM), valproic acid (VPA), and fosphenytoin (fPHT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A status epilepticus model was created with lithium\u2013pilocarpine (5\u00a0mEq\/kg\u2013320\u00a0mg\/kg) in adult male Sprague\u2013Dawley rats with implanted electroencephalography (EEG) electrodes. MDZ (9\u00a0mg\/kg) alone or in dual combinations with antiepileptic drugs (200\u00a0mg\/kg LEV, 50\u00a0mg\/kg LCM, 300\u00a0mg\/kg VPA, 100\u00a0mg\/kg fPHT) was injected i.p. to the experiment groups with status epilepticus. After video\u2010EEG recordings were taken from the rats during and after status, the effects of drug interactions on cognitive and motor behaviors were examined by applying behavioral tests (open field, Rotarod, radial arm maze, and passive avoidance).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with the untreated status epilepticus group, it was determined that MDZ alone and the combination of four antiepileptic drugs administered with MDZ significantly reduced the mortality rate, spike frequency, and spike amplitude of epileptic seizures and suppressed epileptic seizures at certain levels (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.01). Compared to MDZ monotherapy, it was determined that the mortality rate and spike frequency and amplitude decreased significantly in the MDZ\u00a0+\u00a0LCM group (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.01), whereas on the other hand, mortality and spike frequency increased in the MDZ\u00a0+\u00a0LEV group (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.01). No negative effects were observed in learning and memory in all treatment groups, but it was determined that the motor functions of the animals treated with MDZ\u00a0+\u00a0fPHT were impaired compared to both the control group without any treatment and the MDZ group (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In the status epilepticus model induced by lithium\u2013pilocarpine, the combination of MDZ\u00a0+\u00a0LCM was found to be the most effective polytherapy option in reducing seizures and mortality. Additionally, it was observed that LEV, LCM, and VPA administered together with MDZ did not negatively affect both cognitive and motor functions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70546","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T01:39:26Z","timestamp":1747013966000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effective Protection Against Status Epilepticus Caused by Lithium\u2013Pilocarpine: Combination of Midazolam and Lacosamide"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5226-6730","authenticated-orcid":false,"given":"Cumaali","family":"Demirtas","sequence":"first","affiliation":[{"name":"Department of Physiology, Hamidiye Faculty of Medicine University of Health Sciences  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0500-920X","authenticated-orcid":false,"given":"Metehan","family":"Akca","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Tokat Gaziosmanpa\u015fa University  Tokat T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3008-5792","authenticated-orcid":false,"given":"Ugur","family":"Aykin","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hamidiye Faculty of Medicine University of Health Sciences  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunus Emre","family":"Surmeneli","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hamidiye Faculty of Medicine University of Health Sciences  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4234-7155","authenticated-orcid":false,"given":"Hava","family":"Yildirim","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Hamidiye Faculty of Medicine University of Health Sciences  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-5478","authenticated-orcid":false,"given":"Mehmet","family":"Yildirim","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hamidiye Faculty of Medicine University of Health Sciences  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01539.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03056.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNP.0000000000000217"},{"key":"e_1_2_10_5_1","first-page":"191","article-title":"The Effects of Edaravone in Ketamine\u2010Induced Model of Mania in Rats","volume":"76","author":"Arslan F. 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