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Endothelin as a Mediator of Blood-Brain Barrier Function

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New Concepts of a Blood—Brain Barrier

Abstract

Brain capillary endothelial cells (BCEC), the principal components of the blood—brain barrier (BBB) are interconnected by tight junctions, possess polar membranes and a paucity of pinocytotic vesicles in contrast to capillaries in peripheral organs.1 BCEC’s unique features embrace specialized transport and carrier systems as well as enzymes associated with various metabolic pathways that are essential to sustain the dynamic homeostasis of the brain. Many of these processes are thought to be neuronally regulated. There are a number of excellent reviews regarding the specific function of the BBB and regulation of the cerebral circulation by endothelium.2–4 It is now widely accepted that BCEC not only constitute a permeability barrier to ions and organic molecules (e.g., water, electrolytes, proteins, neurotransmitters), but are also an important secretory organ. BCEC produce agents and factors that may be involved in autocrine and paracrine regulation of the microvascular function of the brain. In general, the substances [e.g., prostacyclin, nitric oxide (NO), and adenosine] produced by these cells are considered to be cytoprotective. However, several other agents which are formed in BCEC and when released in excess may impair perfusion, alter BBB permeability and/or mediate cellular injury (i.e., endothelin I, angiotensin II, thromboxane, leukotrienes, platelet—activating factor, and Superoxide radicals). The secretory function of BCEC can also be modulated by substances released from adjacent cellular elements (other vascular cells, blood and/or brain). There is ample evidence that many of these events play a role in regulating vascular tone, permeability, hemostasis and blood pressure under normal conditions. However, in some pathologic conditions an “oversupply” of some of these agents may adversely affect the BBB permeability and/or surface expression of adhesion molecules (i.e., ICAM—1, VCAM—1, P—selectin) which facilitate binding and ultimately extravasation of circulating leukocytes.

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Authors and Affiliations

  1. Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA

    Maria Spatz, Danica Stanimirovic & Richard M. McCarron

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  1. Maria Spatz
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  2. Danica Stanimirovic
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  3. Richard M. McCarron
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Editors and Affiliations

  1. Institute of Ophthalmology, University College London, London, England

    John Greenwood

  2. King’s College, University of London, London, England

    David J. Begley

  3. United Medical and Dental Schools, St. Thomas’ Hospital, London, England

    Malcolm B. Segal

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© 1995 Springer Science+Business Media New York

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Spatz, M., Stanimirovic, D., McCarron, R.M. (1995). Endothelin as a Mediator of Blood-Brain Barrier Function. In: Greenwood, J., Begley, D.J., Segal, M.B. (eds) New Concepts of a Blood—Brain Barrier. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1054-7_5

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  • DOI: https://doi.org/10.1007/978-1-4899-1054-7_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-1056-1

  • Online ISBN: 978-1-4899-1054-7

  • eBook Packages: Springer Book Archive

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