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  3. Empagliflozin demonstrates neuroprotective and cardioprotective effects by reducing ischemia/reperfusion damage in rat models of ischemic stroke and myocardial infarction

Empagliflozin demonstrates neuroprotective and cardioprotective effects by reducing ischemia/reperfusion damage in rat models of ischemic stroke and myocardial infarction

  • Sci Rep. 2025 Mar 15;15(1):8986. doi: 10.1038/s41598-025-93483-7.
Wangde Dai 1 2,  Rashid Alavi 3 4,  Jiajun Li 5,  Juan Carreno 3,  Niema M Pahlevan 3 6 5,  Robert A Kloner 3 6
Affiliations

Affiliations

  • 1 Huntington Medical Research Institutes, HMRI Cardiovascular Research Institute, 686 South Fair Oaks Avenue, Pasadena, CA, 91105, USA. wangdedai@yahoo.com.
  • 2 Division of Cardiovascular Medicine, Department of Medicine of the Keck School of Medicine, University of Southern California, Los Angeles, CA, 90017-2395, USA. wangdedai@yahoo.com.
  • 3 Huntington Medical Research Institutes, HMRI Cardiovascular Research Institute, 686 South Fair Oaks Avenue, Pasadena, CA, 91105, USA.
  • 4 Department of Medical Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA, 91125, USA.
  • 5 Department of Aerospace and Mechanical Engineering, University of Southern California, 3650 McClintock Ave. Room 400, Los Angeles, CA, 90089, USA.
  • 6 Division of Cardiovascular Medicine, Department of Medicine of the Keck School of Medicine, University of Southern California, Los Angeles, CA, 90017-2395, USA.
PMID: 40089564 DOI: 10.1038/s41598-025-93483-7
Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated potential neuroprotective and cardioprotective effects in preliminary studies. This study evaluates the efficacy of empagliflozin (EMPA) in reducing ischemia/reperfusion damage in both the brain and heart using rat models. Ischemic stroke and myocardial infarction (MI) were induced in male Sprague-Dawley rats, which were randomized into three groups: (1) Control (no EMPA), (2) Acute treatment (EMPA, 10 mg/kg IV, administered 10 min before ischemia and 1 min before reperfusion), and (3) Chronic treatment (EMPA, 20 mg/kg in food for 7 days before ischemia). Stroke was induced by middle cerebral artery occlusion (MCAO) for one hour, followed by 3 h of reperfusion, and MI was induced by left coronary artery occlusion for 30 min, followed by 3 h of reperfusion. Brain and heart tissues were analyzed for anatomic size of myocardial infarction and stroke. In the brain, cerebral infarction was significantly smaller in both EMPA treatment groups compared to controls (acute: 3.7 ± 1.2%, chronic: 6.9 ± 2.1% vs. control: 14.5 ± 2.5%, p < 0.05). Edema was also reduced in the EMPA groups (acute: 5.5 ± 0.9%, chronic: 5.9 ± 0.8% vs. control: 9.6 ± 1.2%, p < 0.05). In the heart, MI size was significantly reduced in both EMPA groups (acute: 46.9 ± 2.0%, chronic: 48.8 ± 5.8% vs. control: 70.0 ± 2.6%, p < 0.05), and no-reflow size was smaller in the EMPA groups (acute: 36.3 ± 3.3%, chronic: 33.9 ± 4.3% vs. control: 53.4 ± 3.3%, p < 0.05). EMPA treatment, both acute and chronic, significantly reduces cerebral infarct volume and edema, as well as myocardial infarct size and no-reflow in rat models of ischemic stroke and myocardial ischemia/reperfusion, indicating substantial neuroprotective and cardioprotective effects.

Keywords

Cardioprotective effects; Empagliflozin; Ischemic stroke; Myocardial infarction; Neuroprotection; Sodium-glucose co-transporter 2 inhibitors.

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