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Background <p>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.</p> Methods and results <p>Forty male <i>Sprague-Dawley</i> rats were randomly assigned to four groups: Sham, C/IR, C/IR + Dapa 1&#xa0;mg/kg, and C/IR + Dapa 10&#xa0;mg/kg. The Sham and C/IR groups received vehicle, while the Dapa groups were administered 1 or 10&#xa0;mg/kg orally for one week prior to surgery. Focal cerebral ischemia was induced for 60&#xa0;min, followed by 24&#xa0;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.</p> Conclusions <p>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.</p> Graphical abstract <p></p>

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Dapagliflozin pretreatment attenuates focal cerebral ischemia-reperfusion injury in rats

  • 期刊论文

  • 发表日期：

    2026年6月23日

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  • Asiye Beytur,
  • Engin Korkmaz,
  • Kevser Tanbek,
  • Suat Tekin

摘要

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.

Graphical abstract