Dapagliflozin pretreatment attenuates focal cerebral ischemia-reperfusion injury in rats
Molecular Biology Reports, cilt.53, sa.1, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 53 Sayı: 1
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s11033-026-12191-1
- Dergi Adı: Molecular Biology Reports
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
- Anahtar Kelimeler: Cerebral ischemia, Dapagliflozin, Ischemia reperfusion, Neuroprotective, SGLT2, Stroke
- İnönü Üniversitesi Adresli: Evet
Özet
Background: This study evaluated the prophylactic neuroprotective effects of dapagliflozin (Dapa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in a non-diabetic rat model of cerebral ischemia/reperfusion (C/IR) injury. Methods and results: Forty male Sprague-Dawley rats were randomly assigned to four groups: Sham, C/IR, C/IR + Dapa 1 mg/kg, and C/IR + Dapa 10 mg/kg. The Sham and C/IR groups received vehicle, while the Dapa groups were administered 1 or 10 mg/kg orally for one week prior to surgery. Focal cerebral ischemia was induced for 60 min, followed by 24 h of reperfusion. Outcome assessments included neurological deficit scoring (NDS), behavioral testing, and infarct-area quantification by TTC staining, together with Western blot, ELISA, and oxidative stress analyses. Dapa treatment dose-dependently reduced NDS scores and adhesive-removal time and increased grip strength relative to the C/IR group, and significantly reduced infarct area. At the molecular level, Dapa was associated with increased BDNF, TrkB, p-PI3K, p-Akt, and Bcl-2 and decreased Bax and cleaved caspase-3. Serum levels of the systemic inflammatory mediators IL-1β, IL-6, TNF-α, and NLRP3 were reduced, while tissue antioxidant enzyme activities (SOD, CAT, GSH-Px) were increased and MDA levels decreased. Conclusions: Prophylactic Dapa conferred marked neuroprotection against acute C/IR injury in non-diabetic rats, reducing infarct size and neurological deficit while attenuating oxidative stress, systemic inflammation, and apoptosis. These effects were strongly associated with activation of the BDNF/TrkB/PI3K/Akt survival axis, which represents a promising target for further mechanistic and translational study.