Cation flux through SUR1-TRPM4 and NCX1 in astrocyte endfeet induces water influx through AQP4 and brain swelling after ischemic stroke.

ABSTRACT: Brain swelling causes morbidity and mortality in various brain injuries and diseases but lacks effective treatments. Brain swelling is linked to the influx of water into perivascular astrocytes through channels called aquaporins. Water accumulation in astrocytes increases their volume, which contributes to brain swelling. Using a mouse model of severe ischemic stroke, we identified a potentially targetable mechanism that promoted the cell surface localization of aquaporin 4 (AQP4) in perivascular astrocytic endfeet, which completely ensheathe the brain's capillaries. Cerebral ischemia increased the abundance of the heteromeric cation channel SUR1-TRPM4 and of the Na⁺/Ca²⁺ exchanger NCX1 in the endfeet of perivascular astrocytes. The influx of Na⁺ through SU

SUBMITTER: Stokum JA 

PROVIDER: S-EPMC10369355 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature