Abstract
Ischemic stroke is a serious condition associated with severe functional disability and high mortality, however; effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, has been shown to exert additional non-glycemic benefits including anti-apoptotic effects in different disease settings. Thereby, this study was designed to investigate the ameliorative effect of empagliflozin on the neuronal apoptosis exhibited in cerebral ischemia/reperfusion (I/R) in a rat model targeting HIF-1α/VEGF signaling which is involved in this insult. Global cerebral I/R injury was induced in male Wistar rats through occlusion of the bilateral common carotid arteries for 30 min followed by one-hour reperfusion. Empagliflozin doses of 1 and 10 mg/kg were administered 1 and 24 h after reperfusion. In I/R-injured rats, empagliflozin treatments significantly reduced infarct size and enhanced neurobehavioral functions in a dose-dependent manner. The drug alleviated neuronal death and cerebral injury inflicted by global ischemia as it suppressed neuronal caspase-3 protein expression. In parallel, protein expressions of HIF-1α and its downstream mediator VEGF were upregulated in the ischemic brain following empagliflozin treatment. The results indicated that empagliflozin attenuates cerebral I/R-induced neuronal death via the HIF-1α/VEGF cascade.
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Abdel-latif, R.G., Rifaai, R.A. & Amin, E.F. Empagliflozin alleviates neuronal apoptosis induced by cerebral ischemia/reperfusion injury through HIF-1α/VEGF signaling pathway. Arch. Pharm. Res. 43, 514–525 (2020). https://doi.org/10.1007/s12272-020-01237-y
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DOI: https://doi.org/10.1007/s12272-020-01237-y