Canagliflozin, an Inhibitor of the Na⁺-Coupled D-Glucose Cotransporter, SGLT2, Inhibits Astrocyte Swelling and Brain Swelling in Cerebral Ischemia.

ABSTRACT: Brain swelling is a major cause of death and disability in ischemic stroke. Drugs of the gliflozin class, which target the Na⁺-coupled D-glucose cotransporter, SGLT2, are approved for type 2 diabetes mellitus (T2DM) and may be beneficial in other conditions, but data in cerebral ischemia are limited. We studied murine models of cerebral ischemia with middle cerebral artery occlusion/reperfusion (MCAo/R). Slc5a2/SGLT2 mRNA and protein were upregulated de novo in astrocytes. Live cell imaging of brain slices from mice following MCAo/R showed that astrocytes responded to modest increases in D-glucose by increasing intracellular Na⁺ and cell volume (cytotoxic edema), both of which were inhibited by the SGLT2 inhibitor, canagliflozin. The effect of canagliflozin was

SUBMITTER: Shim B 

PROVIDER: S-EPMC10527352 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature