Therapeutic potential of alpha‑tocopherol in reducing oxidative stress and inflammatory damage after experimental traumatic brain injury and pentylenetetrazol‑induced seizures

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dc.authorid0000-0001-5226-6730
dc.authorid0000-0002-4234-7155
dc.authorid0000-0002-5263-2793
dc.authorid0000-0003-4190-1553
dc.authorid0000-0001-8250-8227
dc.authorid0000-0003-3706-5193
dc.authorid0000-0003-4351-1719
dc.authorid0000-0002-5027-6756
dc.authorid0000-0002-3008-5792
dc.authorid0000-0002-1003-5544
dc.authorid0000-0003-1798-5478
dc.contributor.authorDemirtaş, Cumaali
dc.contributor.authorYıldırım, Hava
dc.contributor.authorDemir, Hüseyin
dc.contributor.authorKıroğlu, Sezin
dc.contributor.authorŞevgin, Kübra
dc.contributor.authorBeyaztaş, Hakan
dc.contributor.authorGüler, Eray Metin
dc.contributor.authorHekimoğlu, Gulam
dc.contributor.authorAykın, Uğur
dc.contributor.authorCoşkunpınar, Ender Mehmet
dc.contributor.authorYıldırım, Mehmet
dc.date.accessioned2026-06-02T13:54:08Z
dc.date.available2026-06-02T13:54:08Z
dc.date.issued2026
dc.departmentFakülteler, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Beyin ve Sinir Cerrahisi Ana Bilim Dalı
dc.description.abstractThe effects of alpha-tocopherol on seizure parameters, locomotor-cognitive functions, inflammatory response, oxidative stress response, histopathological changes, immunohistochemical parameters, and miRNA fold changes were investigated in rats with traumatic brain injury (TBI) and pentylenetetrazol (PTZ)-induced seizures. Sprague–Dawley male rats were randomly divided into three groups: Control (n = 8), TBI + PTZ (n = 10), and TBI + PTZ + tocopherol (n = 10). 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 + PTZ groups for 6 days, while 500 mg/kg alpha-tocopherol was administered intraperitoneally to the TBI + PTZ + tocopherol group. Seizure intensity, sei zure frequency, and total seizure duration were significantly reduced in the TBI + PTZ + tocopherol group compared to the TBI + PTZ group (p < 0.05). No significant adverse effects related to TBI and PTZ were observed in the animals’ locomotor activity, anxiety-like behaviors, or learning and memory test outcomes. In the TBI + PTZ + tocopherol group, significant reductions were observed in inflammatory cytokine response, oxidative stress, and SUR1-TRPM4 channel activity compared to the TBI + PTZ group (p < 0.001). 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 + PTZ + tocopherol group, downregulated miR-324-5p increased (p < 0.05). 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, hippocam pus, 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.
dc.identifier.citationDemirtaş, C., Yıldırım, H., Demir, H., Kıroğlu, S., Şevgin, K., Beyaztaş, H., Güler, E. M., Hekimoğlu, G., Aykın, U., Coşkunpınar, E. M., & Yıldırım, M. (2026). Therapeutic potential of alpha‑tocopherol in reducing oxidative stress and inflammatory damage after experimental traumatic brain injury and pentylenetetrazol‑induced seizures. Naunyn-Schmiedeberg's Archives of Pharmacology, https://doi.org/10.1007/s00210-026-05442-2
dc.identifier.doi10.1007/s00210-026-05442-2
dc.identifier.issn1432-1912
dc.identifier.issn0028-1298
dc.identifier.pmidPMID: 42154014
dc.identifier.scopus2-s2.0-105039483189
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1007/s00210-026-05442-2
dc.identifier.urihttps://hdl.handle.net/20.500.13055/1493
dc.identifier.wosWOS:001770045800001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherSCI-E - Science Citation Index Expanded
dc.institutionauthorDemir, Hüseyin
dc.institutionauthorid0000-0002-5263-2793
dc.language.isoen
dc.publisherSpringer Nature Link
dc.relation.ispartofNaunyn-Schmiedeberg's Archives of Pharmacology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectTraumatic Brain Injury
dc.subjectPentylenetetrazol-Induced Seizures
dc.subjectAlpha-Tocopherol
dc.subjectOxidative Stress
dc.subjectMiRNA
dc.titleTherapeutic potential of alpha‑tocopherol in reducing oxidative stress and inflammatory damage after experimental traumatic brain injury and pentylenetetrazol‑induced seizures
dc.typeArticle
dspace.entity.typePublication

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