The role of the blood-brain barrier Na-K-2Cl cotransporter in stroke.
Studies from this and other laboratories have shown that the Na-K-2Cl cotransporter is present in BBB endothelial cells is stimulated by factors present during cerebral ischemia. Further, our in situ studies have shown that the cotransporter resides predominantly in the luminal BBB membrane. This is consistent with the hypothesis that a luminal cotransporter works with abluminal Na/K ATPase to secrete NaCl into the brain, and during stroke, BBB cotransporter activity is increased such that the barrier hypersecretes NaCl and water into the brain, facilitating cytotoxic edema formation. Our in vivo MCAO stroke studies provide further support for a role of the BBB cotransporter in cerebral ede-ma formation. Collectively, these findings suggest that the BBB Na-K-2Cl cotransporter does indeed substantially contribute to cerebral edema formation in stroke.
O'Donnell
Martha E
ME
Department of Physiology and Membrane Biology, University of California, One Shields Ave., Davis, CA 95616, USA. meodonnell@ucdavis.edu
Lam
Tina I
TI
Tran
Lien
L
Anderson
Steven E
SE
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D001929:Brain Edema / Q000188:drug therapy; D002545:Brain Ischemia / Q000188:drug therapy; D002034:Bumetanide / Q000494:pharmacology / Q000627:therapeutic use; D002544:Cerebral Infarction / Q000188:drug therapy; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism*
D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide