Alpha-syntrophin deletion removes the perivascular but not endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia.

Mahmood Amiry-Moghaddam, Rong Xue, Finn Mogens Haug, John D. Neely, Anish Bhardwaj, Peter Agre, Marvin E. Adams, Stanley C. Froehner, Susumu Mori, Ole P. Ottersen

Research output: Contribution to journalArticle

183 Citations (Scopus)

Abstract

The formation of brain edema, commonly occurring as a potentially lethal complication of acute hyponatremia, is delayed following knockout of the water channel aquaporin-4 (AQP4). Here we show by high-resolution immunogold analysis of the blood-brain-barrier that AQP4 is expressed in brain endothelial cells as well as in the perivascular membranes of astrocyte endfeet. A selective removal of perivascular AQP4 by alpha-syntrophin deletion delays the buildup of brain edema (assessed by Diffusion-weighted MRI) following water intoxication, despite the presence of a normal complement of endothelial AQP4. This indicates that the perivascular membrane domain, which is peripheral to the endothelial blood-brain barrier, may control the rate of osmotically driven water entry. This study is also the first to demonstrate that the time course of edema development differs among brain regions, probably reflecting differences in aquaporin-4 distribution. The resolution of the molecular basis and subcellular site of osmotically driven brain water uptake should help design new therapies for acute brain edema.

Original languageEnglish (US)
Pages (from-to)542-544
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume18
Issue number3
StatePublished - 2004
Externally publishedYes

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Aquaporin 4
Hyponatremia
Brain Edema
Blood-Brain Barrier
Brain
Theoretical Models
Water Intoxication
Water
Aquaporins
Diffusion Magnetic Resonance Imaging
Membranes
Astrocytes
Endothelial cells
Edema
Magnetic resonance imaging
Endothelial Cells
syntrophin alpha1

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Alpha-syntrophin deletion removes the perivascular but not endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia. / Amiry-Moghaddam, Mahmood; Xue, Rong; Haug, Finn Mogens; Neely, John D.; Bhardwaj, Anish; Agre, Peter; Adams, Marvin E.; Froehner, Stanley C.; Mori, Susumu; Ottersen, Ole P.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 18, No. 3, 2004, p. 542-544.

Research output: Contribution to journalArticle

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