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The Blood Brain Barrier and Inflammation pp 187–211Cite as

Pathways Across the Blood-Brain Barrier

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Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

The parenchymal blood-brain barrier (BBB) is formed by highly specialized vascular endothelial cells of the central nervous system (CNS). As part of the neurovascular unit (NVU), the BBB builds up a tight barrier between the changing milieu of the bloodstream and the vulnerable CNS. Yet, during inflammatory diseases of the CNS, immune cells are recruited into the CNS and thus migrate across the inflamed BBB. In particular, effector T (Teff) cells critically contribute to autoimmune neuroinflammation such as multiple sclerosis (MS). Extravasation of Teff cells across the inflamed BBB is a well-coordinated multistep process tightly regulated through cell adhesion molecules, chemotactic factors, and their receptors. An initial contact between the circulating Teff cell and the inflamed endothelial cells of the BBB mediates slowing down of Teff cells. Then, integrins on the Teff cell surface acquire an activated conformation. This in turn is prerequisite for shear-resistant arrest that transforms into firm adhesion, crawling, and finally diapedesis. Following diapedesis, Teff cells accumulate in the perivascular space between the two basement membranes of the NVU. Only after reactivation with their cognate antigen by antigen-presenting cells (APCs), Teff cells can breach the parenchymal basement membrane and infiltrate the CNS parenchyma. Interfering with pathological Teff cell recruitment into the CNS has been successfully translated into the clinic for the treatment of MS patients through natalizumab, which blocks extravasation of immune cells across the BBB. This review introduces the molecular players and discusses the cellular pathway of Teff cell extravasation across the inflamed BBB.

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Acknowledgment

We thankfully acknowledge financial support by the Swiss Multiple Sclerosis Society, Zürich, Switzerland, and the Foundation for Clinical and Experimental Cancer Research, Bern, Switzerland, to RL. MA was supported by Swiss National Science Foundation Early Postdoc Mobility Fellowship. We are grateful to Gaby Enzmann for critical reading of the manuscript.

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  1. Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA

    Michael Abadier

  2. Theodor Kocher Institute, University of Bern, Freiestrasse 1, 3012, Bern, Switzerland

    Ruth Lyck

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  1. Theodor Kocher Institute, University of Bern, Bern, Switzerland

    Ruth Lyck

  2. Theodor Kocher Institute, University of Bern, Bern, Switzerland

    Gaby Enzmann

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Abadier, M., Lyck, R. (2017). Pathways Across the Blood-Brain Barrier. In: Lyck, R., Enzmann, G. (eds) The Blood Brain Barrier and Inflammation. Progress in Inflammation Research. Springer, Cham. https://doi.org/10.1007/978-3-319-45514-3_9

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