Research article summary (published 15 Jun 2009):

Loss of astrocyte polarity marks blood-brain barrier impairment during experimental autoimmune encephalomyelitis.

Full Abstract

In multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE), dysfunction of the blood-brain barrier (BBB) leads to edema formation within the central nervous system. The molecular mechanisms of edema formation in EAE/MS are poorly understood. We hypothesized that edema formation is due to imbalanced water transport across the BBB caused by a disturbed crosstalk between BBB endothelium and astrocytes. Here, we demonstrate at the light microscopic and ultrastructural level, the loss of polarized localization of the water channel protein aquaporin-4 (AQP4) in astrocytic endfeet surrounding microvessels during EAE. AQP4 was found to be redistributed over the entire astrocytic cell surface and lost its arrangement in orthogonal arrays of intramembranous particles as seen in the freeze-fracture replica. In addition, immunostaining for the astrocytic extracellular matrix receptor beta-dystroglycan disappeared from astroglial membranes in the vicinity of inflammatory cuffs, whereas immunostaining for the dystroglycan ligands agrin and laminin in the perivascular basement membrane remained unchanged. Our data suggest that during EAE, loss of beta-dystroglycan-mediated astrocyte foot process anchoring to the basement membrane leads to loss of polarized AQP4 localization in astrocytic endfeet, and thus to edema formation in EAE.

Author information

Author/s: Wolburg-Buchholz, Karen (K); Mack, Andreas F (AF); Steiner, Esther (E); Pfeiffer, Friederike (F); Engelhardt, Britta (B); Wolburg, Hartwig (H);

Affiliation: Institute of Pathology, University of Tübingen, Liebermeisterstrasse 8, 72076 Tübingen, Germany.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Acta neuropathologica (Acta Neuropathol), published in Germany. (Language: eng)

Reference: 2009-Aug; vol 118 (issue 2) : pp 219-33

Dates: Created 2009/07/07; Completed 2009/08/19; Revised 2009/10/08;

PMID: 19533155, status: MEDLINE (last retrieval date: 10/8/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

ErratumIn: Acta Neuropathol. 2009 Oct;118(4):583.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - metabolism Animals Aquaporin 4 - metabolism Astrocytes - metabolism; pathology Blood-Brain Barrier - metabolism; pathology Brain Edema - etiology; metabolism Cell Polarity

Dystroglycans - metabolism Encephalomyelitis, Autoimmune, Experimental - complications; metabolism; pathology Female Immunohistochemistry Mice Microscopy, Confocal Microscopy, Electron, Transmission

Associated Chemicals: Agrin (0) ; Aqp4 protein, mouse (0) ; Aquaporin 4 (0) ; Dystroglycans (146888-27-9)

Related articles

These are the highest related articles currently in the database:

• Enhanced expression of aquaporin 4 in human brain with inflammatory diseases. 24 Aug 2005
• Molecular basis of bilirubin-induced neurotoxicity. 30 Jan 2004
• Gliosis in the spinal cords of rats with experimental allergic encephalomyelitis: immunostaining of carbonic anhydrase and vimentin in reactive astrocytes. 30 Dec 1988
• Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. 26 Mar 2008
• Flavonoids influence monocytic GTPase activity and are protective in experimental allergic encephalitis. 18 Dec 2004
• Increased caveolin-1 expression precedes decreased expression of occludin and claudin-5 during blood-brain barrier breakdown. 7 Aug 2007
• Block of neural Kv1.1 potassium channels for neuroinflammatory disease therapy. 30 Oct 2006
• Normobaric hyperoxia inhibits NADPH oxidase-mediated matrix metalloproteinase-9 induction in cerebral microvessels in experimental stroke. 9 Sep 2008
• Aquaporin-4 in hepatic encephalopathy. 29 Nov 2007
• Angiopoietin1/Tie2 and VEGF/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke. 12 Mar 2007

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.