Şeker, UğurGunara, Sezer OnurAkgun, Mehmet YigitSeker, UgurUcar, Ege AnilAtes, OzkanBasar, IbrahimDepartment of Basic Medical Sciences / Temel Tıp Bilimleri Bölümü10. Faculty of Medicine / Tıp Fakültesi01. Mardin Artuklu University / Mardin Artuklu Üniversitesi2025-07-152025-07-1520251664-2295https://doi.org/10.3389/fneur.2025.1551449https://hdl.handle.net/20.500.12514/9049Objective This study investigated the neuroprotective effects of melatonin in mice subjected to traumatic brain injury (TBI), focusing on caspase-dependent apoptotic signaling pathways.Materials and methods A total of 21 mice were divided into three groups: control, trauma (TBI), and trauma + melatonin (TBI + M). TBI was induced in the TBI and TBI + M groups via a free-fall impact on the frontal lobes. A single dose of 10 mg/kg of melatonin was intraperitoneally administered to the TBI + M group. Brain tissues were collected for histological evaluation and immunohistochemical analysis of apoptotic proteins.Results The control group showed normal brain morphology, while the trauma group exhibited significant tissue loss and demyelination. The TBI + M group demonstrated reduced demyelination compared to the trauma group. An immunohistochemical analysis revealed increased expression of Bax and decreased expression of Bcl-2 in the trauma group, both of which were mitigated by melatonin treatment. The expression levels of caspase-3 and caspase-9 were elevated in the trauma group, whereas the TBI + M group showed expression levels comparable to the control group.Conclusion TBI increased apoptotic protein expression, indicating neurodegeneration. The administration of melatonin at 10 mg/kg attenuated TBI-induced apoptosis and demyelination while promoting anti-apoptotic protein expression in the experimental model. These findings suggest a potential therapeutic role for melatonin in the management of TBI.en10.3389/fneur.2025.1551449info:eu-repo/semantics/closedAccessTraumatic Brain InjuryMelatoninApoptosisNeurodegenerationMiceNeuroprotection Unveiled: Melatonin Mitigates Apoptotic Pathways in Traumatic Brain InjuryArticle16Q2Q2WOS:0015037527000012-s2.0-10500753742540492170