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

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An Erratum to this article was published on 07 August 2009

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 β-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 β-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.

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Acknowledgments

The expert technical assistance of Therese Périnat is acknowledged. We thank Ria Knittel for skilful help with freeze-fracturing and Gabi Frommer-Kästle with ultrathin sectioning. This study was funded by the Hertie Foundation Germany (grant 1.01.1/07/003) to HW and BE and by the Theodore Ott Foundation to BE.

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Authors and Affiliations

  1. Institute of Pathology, University of Tübingen, Liebermeisterstraße 8, 72076, Tübingen, Germany

    Karen Wolburg-Buchholz & Hartwig Wolburg

  2. Institute of Anatomy, University of Tübingen, 72076, Tübingen, Germany

    Andreas F. Mack

  3. Theodor Kocher Institute, University of Bern, 3012, Bern, Switzerland

    Esther Steiner, Friederike Pfeiffer & Britta Engelhardt

Authors
  1. Karen Wolburg-Buchholz
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  2. Andreas F. Mack
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  3. Esther Steiner
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  4. Friederike Pfeiffer
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  5. Britta Engelhardt
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  6. Hartwig Wolburg
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Corresponding author

Correspondence to Hartwig Wolburg.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00401-009-0579-z

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Wolburg-Buchholz, K., Mack, A.F., Steiner, E. et al. Loss of astrocyte polarity marks blood–brain barrier impairment during experimental autoimmune encephalomyelitis. Acta Neuropathol 118, 219–233 (2009). https://doi.org/10.1007/s00401-009-0558-4

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  • DOI: https://doi.org/10.1007/s00401-009-0558-4

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