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Updated: Jun 22, 2026
Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019
Loss of astrocyte polarity marks blood-brain barrier impairment during experimental autoimmune encephalomyelitis
Karen Wolburg-Buchholz1, Andreas F Mack, Esther Steiner
1Institute of Pathology, University of Tübingen, Liebermeisterstrasse 8, 72076 Tübingen, Germany.
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.
Insights
In experimental autoimmune encephalomyelitis (EAE), astrocyte dysfunction disrupts water transport across the blood-brain barrier (BBB). This leads to aquaporin-4 (AQP4) mislocalization and central nervous system edema in EAE/MS.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Blood-brain barrier (BBB) dysfunction in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), causes central nervous system (CNS) edema.
- The precise molecular mechanisms driving edema formation in EAE/MS remain unclear.
Purpose of the Study:
- To investigate the molecular mechanisms of edema formation in EAE, focusing on water transport and astrocyte-endothelial cell interactions.
- To determine the role of aquaporin-4 (AQP4) localization and astrocyte-basement membrane interactions in EAE-induced edema.
Main Methods:
- Light and electron microscopy to examine BBB structure and protein localization in EAE.
- Freeze-fracture electron microscopy to analyze AQP4 arrangement in astrocytic endfeet.
- Immunostaining to assess the expression and localization of beta-dystroglycan, agrin, and laminin.
Main Results:
- Loss of polarized aquaporin-4 (AQP4) localization in astrocytic endfeet surrounding microvessels during EAE.
- AQP4 redistribution across the entire astrocytic cell surface, with loss of orthogonal arrays.
- Disappearance of beta-dystroglycan from astroglial membranes near inflammatory cuffs, while basement membrane ligands remained unchanged.
Conclusions:
- Loss of beta-dystroglycan-mediated astrocyte anchoring to the basement membrane contributes to AQP4 mislocalization.
- Impaired astrocyte-BBB interactions and altered water transport are key factors in EAE/MS edema formation.
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