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Sprague\u2013Dawley male rats were randomly divided into three groups: Control (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098), TBI\u2009+\u2009PTZ (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910), and TBI\u2009+\u2009PTZ\u2009+\u2009tocopherol (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910). After inducing TBI in animals using the weight-drop method, increased post-injury seizure susceptibility was achieved by administering subconvulsive doses of PTZ. Saline was administered intraperitoneally to the control and TBI\u2009+\u2009PTZ groups for 6\u00a0days, while 500\u00a0mg\/kg alpha-tocopherol was administered intraperitoneally to the TBI\u2009+\u2009PTZ\u2009+\u2009tocopherol group. Seizure intensity, seizure frequency, and total seizure duration were significantly reduced in the TBI\u2009+\u2009PTZ\u2009+\u2009tocopherol group compared to the TBI\u2009+\u2009PTZ group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). No significant adverse effects related to TBI and PTZ were observed in the animals\u2019 locomotor activity, anxiety-like behaviors, or learning and memory test outcomes. In the TBI\u2009+\u2009PTZ\u2009+\u2009tocopherol group, significant reductions were observed in inflammatory cytokine response, oxidative stress, and SUR1-TRPM4 channel activity compared to the TBI\u2009+\u2009PTZ group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). While degenerative and apoptotic neurons and the number of 8-OHdG-positive cells in the CA1 and dentate gyrus regions were limited in the TBI\u2009+\u2009PTZ\u2009+\u2009tocopherol group, downregulated miR-324-5p increased (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Alpha-tocopherol reduced the severity and duration of seizures, reduced oxidative stress and inflammation, and stabilized the thiol-disulfide balance. It also reduced degenerative cell structures and DNA damage in the cortex, hippocampus, and dentate gyrus. In conclusion, the findings of this study suggest that alpha-tocopherol is a potential neuroprotective agent that modulates early epileptogenic network instability in TBI and seizure susceptibility through multiple pathways, including oxidative stress, inflammation, and ion channel regulation.\n                  <\/jats:p>","DOI":"10.1007\/s00210-026-05442-2","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:40:35Z","timestamp":1779169235000},"page":"17193-17215","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic potential of alpha-tocopherol in reducing oxidative stress and inflammatory damage after experimental traumatic brain injury and pentylenetetrazol-induced seizures"],"prefix":"10.1007","volume":"399","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5226-6730","authenticated-orcid":false,"given":"Cumaali","family":"Demirtas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4234-7155","authenticated-orcid":false,"given":"Hava","family":"Yildirim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5263-2793","authenticated-orcid":false,"given":"Huseyin","family":"Demir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4190-1553","authenticated-orcid":false,"given":"Sezin","family":"Kiroglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8250-8227","authenticated-orcid":false,"given":"Kubra","family":"Sevgin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3706-5193","authenticated-orcid":false,"given":"Hakan","family":"Beyaztas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4351-1719","authenticated-orcid":false,"given":"Eray Metin","family":"Guler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5027-6756","authenticated-orcid":false,"given":"Gulam","family":"Hekimoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3008-5792","authenticated-orcid":false,"given":"Ugur","family":"Aykin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1003-5544","authenticated-orcid":false,"given":"Ender Mehmet","family":"Coskunpinar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-5478","authenticated-orcid":false,"given":"Mehmet","family":"Yildirim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"issue":"3","key":"5442_CR1","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1177\/1545968309348318","volume":"24","author":"A Wu","year":"2010","unstructured":"Aiguo Wu, Zhe Ying, Gomez-Pinilla F (2010) Vitamin E protects against oxidative damage and learning disability after mild traumatic brain injury in rats Neurorehabil Neural Repair 24 3 290 298 https:\/\/doi.org\/10.1177\/1545968309348318","journal-title":"Neurorehabil Neural Repair"},{"issue":"12","key":"5442_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122107","volume":"17","author":"P Ambrogini","year":"2016","unstructured":"Ambrogini P, Betti M, Galati C, Di Palma M,  Lattanzi D, Savelli D, Galli F, Cuppini R, Minelli A (2016) \u03b1-Tocopherol and hippocampal neural plasticity in physiological and pathological conditions. 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