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Immune-vascular mural cell interactions: consequences for immune cell trafficking, cerebral blood flow, and the blood-brain barrier

Barkaway, Anna; Attwell, David; Korte, Nils; (2022) Immune-vascular mural cell interactions: consequences for immune cell trafficking, cerebral blood flow, and the blood-brain barrier. Neurophotonics , 9 (3) , Article 031914. 10.1117/1.NPh.9.3.031914. Green open access

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Abstract

Brain barriers are crucial sites for cerebral energy supply, waste removal, immune cell migration, and solute exchange, all of which maintain an appropriate environment for neuronal activity. At the capillary level, where the largest area of brain-vascular interface occurs, pericytes adjust cerebral blood flow (CBF) by regulating capillary diameter and maintain the blood-brain barrier (BBB) by suppressing endothelial cell (EC) transcytosis and inducing tight junction expression between ECs. Pericytes also limit the infiltration of circulating leukocytes into the brain where resident microglia confine brain injury and provide the first line of defence against invading pathogens. Brain "waste" is cleared across the BBB into the blood, phagocytosed by microglia and astrocytes, or removed by the flow of cerebrospinal fluid (CSF) through perivascular routes-a process driven by respiratory motion and the pulsation of the heart, arteriolar smooth muscle, and possibly pericytes. "Dirty" CSF exits the brain and is probably drained around olfactory nerve rootlets and via the dural meningeal lymphatic vessels and possibly the skull bone marrow. The brain is widely regarded as an immune-privileged organ because it is accessible to few antigen-primed leukocytes. Leukocytes enter the brain via the meninges, the BBB, and the blood-CSF barrier. Advances in genetic and imaging tools have revealed that neurological diseases significantly alter immune-brain barrier interactions in at least three ways: (1) the brain's immune-privileged status is compromised when pericytes are lost or lymphatic vessels are dysregulated; (2) immune cells release vasoactive molecules to regulate CBF, modulate arteriole stiffness, and can plug and eliminate capillaries which impairs CBF and possibly waste clearance; and (3) immune-vascular interactions can make the BBB leaky via multiple mechanisms, thus aggravating the influx of undesirable substances and cells. Here, we review developments in these three areas and briefly discuss potential therapeutic avenues for restoring brain barrier functions.

Type: Article
Title: Immune-vascular mural cell interactions: consequences for immune cell trafficking, cerebral blood flow, and the blood-brain barrier
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1117/1.NPh.9.3.031914
Publisher version: https://doi.org/10.1117/1.NPh.9.3.031914
Language: English
Additional information: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Keywords: blood–brain barrier, cerebral blood flow, immune–vascular interactions, leukocytes, pericytes, waste clearance
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10149609
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