Korkmaz, EnginBeytur, AsiyeErden, YavuzTanbek, KevserTekin, CigdemTekin, Suat2026-04-042026-04-0420250364-31901573-6903https://doi.org/10.1007/s11064-025-04629-yhttps://hdl.handle.net/11616/109833Ischemic stroke (IS) is a leading cause of death and permanent disability worldwide. Diabetes is a major risk factor for IS and independently increases mortality. This study investigated the neuroprotective effects of Myrtenal (Myrt) in a rat model of IS under both diabetic and non-diabetic conditions. Sprague Dawley rats received Myrt (40 mg/kg, intraperitoneally) for 28 days before undergoing 60-minute middle cerebral artery occlusion followed by 24 h of reperfusion. Neurological outcomes were assessed using behavioral tests, infarct volume was measured by TTC staining, and biochemical analyses evaluated oxidative stress (MDA, SOD, CAT, GSH-Px) and inflammatory markers (NLRP3, TNF-alpha, IL-6, IL-1 beta). Western blotting was performed to examine BDNF/TrkB, p-PI3K/p-Akt signaling, and apoptosis-related proteins (Caspase-3, Bcl-2, Bax). IS impaired neurological function and increased infarct size, apoptosis, inflammation, and lipid peroxidation, while reducing antioxidant enzymes and BDNF/TrkB and p-PI3K/p-Akt levels (p < 0.05). These pathological changes were more severe in diabetic rats. Pretreatment with Myrt significantly ameliorated these effects in both diabetic and non-diabetic groups (p < 0.05). These findings suggest that Myrt exerts neuroprotective effects against IS by suppressing inflammation, oxidative stress, and apoptosis, possibly through modulation of BDNF/TrkB and p-PI3K/p-Akt pathways. These findings indicate that Myrt may possess neuroprotective potential in IS under both hyperglycemic and normoglycemic conditions.eninfo:eu-repo/semantics/closedAccessMyrtenalIschemic strokeDiabetes mellitusIschemia reperfusion injuryPI3KAktArticle5114140576910.1007/s11064-025-04629-y2-s2.0-105025062351Q1WOS:001641909100001Q20000-0002-2807-60960000-0001-9038-19240000-0002-8365-29140000-0003-2099-2273