Abstract 4364551: Post-Ischemic Administration of Empagliflozin Reduces Cerebral Infarction but Not Edema in a Rat Ischemic Stroke Model

Abstract

Background: We previously reported that empagliflozin (EMPA), a sodium-glucose co-transporter 2 inhibitor, significantly reduced infarct size and cerebral edema in a rat model of ischemic stroke when administered either chronically via oral route for 7 days prior to middle cerebral artery occlusion (MCAO) or given IV acutely 10 minutes before MCAO (doi: 10.1038/s41598-025-93483-7). This is clinically relevant for patients already receiving this drug for diabetes, heart failure, or other indications. However, the vast majority of individuals presenting with acute stroke are unlikely to be on EMPA at the time of stroke onset. The neuroprotective potential of EMPA when administered after stroke onset remains unclear. Therefore, we investigated the effect of post-stroke EMPA administration on infarct size following MCAO. Methods: Male Sprague-Dawley rats were randomly assigned to (1) control group, receiving intravenous saline 10 minutes after MCAO (n =13); and (2) acute EMPA group, treated with EMPA (20 mg/kg, IV, n = 12) at the same post-occlusion time point. Transient focal cerebral ischemia was induced by intraluminal filament occlusion of the MCA for 60 minutes, followed by a 3-hour reperfusion period. Brain tissues were then collected and sectioned for 2,3,5-triphenyltetrazolium chloride (TTC) staining to quantify cerebral infarct and edema volumes. Results: Rats treated with EMPA post-MCAO exhibited significantly reduced infarct volumes (4.89 ± 1.02% of total brain volume) compared to controls (9.99 ± 1.59%, p = 0.0137). However, there was no significant difference in cerebral edema between groups: 6.93 ± 0.91% in the EMPA group versus 7.84 ± 0.81% in controls (p = 0.463). Conclusion: This study shows that a single intravenous dose of EMPA administered 10 minutes after MCAO effectively reduces cerebral infarction but does not impact edema formation in a rat model of stroke.