{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:45:46Z","timestamp":1790707546072,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Besides seizures, a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy, which further debilitates their quality of life. This study provides an in\u2010depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20\u2009mg\/kg doses, respectively, on corneal kindling\u2010induced generalized seizures and behavioral alterations. Furthermore, observed convulsive frequency and behavioral changes were correlated to post\u2010kindling\u2010induced changes in the activity of markers of oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult C57BL\/6 mice were kindled via twice\u2010daily transcorneal 50\u2010Hz electrical stimulations (3\u2009mA) for 3\u2009s for 12\u2009days until animals reached a fully kindled state. After the kindling procedure, animals were tested using a set of behavioral tests, and neurochemical alterations were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Corneal\u2010kindled animals exhibited intense generalized convulsions, altered behavioral phenotypes typified by positive symptoms (hyperlocomotion), negative symptoms (anxiety and anhedonia), and deficits in semantic and working memory. BRV 10\u2009+\u2009RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4\u20135 seizures and improved phenotypical deficits, that is, anxiety, depression, and memory impairments. Moreover, this combination therapy mitigated kindling\u2010induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Based on our outcomes, this dual therapy provides supporting evidence in alleviating epilepsy\u2010induced neurobehavioral comorbidities and changes in redox homeostasis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12478","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T05:06:21Z","timestamp":1729659981000},"page":"209-221","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Brivaracetam and rufinamide combination increased seizure threshold and improved neurobehavioral deficits in corneal kindling model of epilepsy"],"prefix":"10.1002","volume":"8","author":[{"given":"Awais","family":"Sattar","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Bahauddin Zakariya University  Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohabia","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Bahauddin Zakariya University  Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hammad","family":"Murtaza","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Bahauddin Zakariya University  Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2295-6049","authenticated-orcid":false,"given":"Waseem","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Bahauddin Zakariya University  Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanveer","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Institut pour l'Avanc\u00e9e des Biosciences, Centre de Recherche UGA\/INSERM U1209\/CNRS 5309 Universit\u00e9 Grenoble Alpes  Saint Martin d'H\u00e8res France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faleh","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1337-8574","authenticated-orcid":false,"given":"Imran","family":"Imran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Bahauddin Zakariya University  Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022426"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.120.019539"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnetp.2023.1338864"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054848"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/157015909788848929"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2227-7"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb05815.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1992.67.2.443"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2014.02.013"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756285617742081"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213677"},{"key":"e_1_2_11_13_1","first-page":"6509","article-title":"Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures","volume":"9","author":"Mumoli L","year":"2015","journal-title":"Drug Des Devel Ther"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01552.x"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(99)00062-5"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(98)00016-3"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114406"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2013.05.035"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15030666"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2020.108831"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2022.173387"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.08.060"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-198-7_2"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2015.04.001"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2014.11.018"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/jaoac\/77.5.1308"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2016.135"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f25b16"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2017.03.003"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1535-7511.2006.00125.x"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.2174\/157015909788848866"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.836321"},{"key":"e_1_2_11_33_1","first-page":"165","article-title":"Neuropsychiatric disease and treatment dovepress anxiety disorders and gaba neurotransmission: a disturbance of modulation","volume":"11","author":"Nuss P","year":"2015","journal-title":"Neuropsychiatr Dis Treat"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0200-23.2023"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.4c00962"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2015.0739"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.878991"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.107445"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-015-0110-9"},{"issue":"1","key":"e_1_2_11_40_1","first-page":"68","article-title":"The neurobiology of anhedonia and other reward\u2010related deficits","volume":"35","author":"Der\u2010Avakian A","year":"2012","journal-title":"Neuroscience"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1535-7597.2005.05106.x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-008-0189-x"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2019.04.021"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1159\/000296139"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11010157"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/795259"}],"container-title":["Animal Models and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.12478","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T09:36:50Z","timestamp":1741772210000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ame2.12478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":45,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/ame2.12478"],"URL":"https:\/\/doi.org\/10.1002\/ame2.12478","archive":["Portico"],"relation":{},"ISSN":["2576-2095","2576-2095"],"issn-type":[{"value":"2576-2095","type":"print"},{"value":"2576-2095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,22]]},"assertion":[{"value":"2024-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}