Dapagliflozin pretreatment attenuates focal cerebral ischemia-reperfusion injury in rats.

backgroundThis 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

resultsForty 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.

conclusionsProphylactic 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.