Demirtaş, CumaaliYıldırım, HavaDemir, HüseyinKıroğlu, SezinŞevgin, KübraBeyaztaş, HakanGüler, Eray MetinHekimoğlu, GulamAykın, UğurCoşkunpınar, Ender MehmetYıldırım, Mehmet2026-06-022026-06-022026Demirtaş, 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/s00210-026-05442-21432-19120028-1298https://doi.org/10.1007/s00210-026-05442-2https://hdl.handle.net/20.500.13055/1493The 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.eninfo:eu-repo/semantics/openAccessTraumatic Brain InjuryPentylenetetrazol-Induced SeizuresAlpha-TocopherolOxidative StressMiRNAArticle10.1007/s00210-026-05442-2Q2WOS:0017700458000012-s2.0-105039483189PMID: 42154014Q2