Abstract 4141798: Empagliflozin dramatically reduced stroke size and cerebral edema in a rat model

Background: Ischemic stroke is associated with high mortality, morbidity and disability that significantly affects the quality of life of patients even in the current thrombolytic/thrombectomy era. The effect of empagliflozin (EMPA), a sodium glucose co-transporter 2 inhibitor on stroke is unknown. Methods: Male SD rats were randomized into three groups (n = 10 in each group): (1) Control group: rats received regular diet alone (without EMPA); (2) Acute treatment group: EMPA (10 mg/kg, IV) given at 10 minutes prior to middle cerebral artery occlusion (MCAO) and one minute prior to reperfusion; (3) Chronic treatment group: EMPA given by food (20 mg/kg) for 7 days before MCAO. A standard intraluminal filament MCAO was performed for one hour of MCA occlusion followed by 3 hours of reperfusion. The brain was harvested and sliced for 2,3,5-triphenyltetrazolium chloride (TTC) staining to measure the volume of cerebral infarction and edema using the technique of Regoldi. Results: The size of the cerebral infarction, expressed as percentage (%) of the infarct volume to the whole brain volume, was significantly smaller in the acute EMPA treatment group (2.8 ± 1.2%) and chronic EMPA group (7.3 ± 2.7%) compared with the control group (16.7 ± 3.2%; p = 0.002) (Figure). The edema of the ipsilateral hemisphere, expressed as percentage of the edema volume to the contralateral hemisphere volume (%), was significantly reduced in the acute EMPA group (4.6 ± 0.9%) and chronic EMPA group (5.2 ± 0.7%) compared to the control group (11.2 ± 1.5%; p = 0.001). Conclusion: Our data indicates that EMPA significantly reduced cerebral infarction and edema in a stroke model in rats. Acute IV EMPA reduced stroke size by 83%.