Pericytes regulate the blood–brain barrier

Abstract

The blood-brain barrier (BBB) consists of specific physical barriers, enzymes and transporters, which together maintain the necessary extracellular environment of the central nervous system (CNS). The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport. Other possible constituents of the BBB include extracellular matrix, astrocytes and pericytes, but the relative contribution of these different components to the BBB remains largely unknown. Here we demonstrate a direct role of pericytes at the BBB in vivo. Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased permeability occurs by endothelial transcytosis, a process that is rapidly arrested by the drug imatinib. Furthermore, we show that pericytes function at the BBB in at least two ways: by regulating BBB-specific gene expression patterns in endothelial cells, and by inducing polarization of astrocyte end-feet surrounding CNS blood vessels. Our results indicate a novel and critical role for pericytes in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the BBB.

Accelerated pericyte degeneration and blood–brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer’s disease

“…The tissue sections were blocked in 5% donkey serum (Jackson ImmunoResearch, West Grove, PA, USA) containing 0.05% Triton X-100 (Sigma-Aldrich, St Louis, MO, USA) and then incubated with the following primary antibodies overnight at 4 C: goat antihuman PDGFR (1:100, R&D Systems, Minneapolis, MN, USA) to detect pericyte marker PDGFR , [3][4][5][6] rabbit anti-human fibrinogen (1:500, Dako), goat anti-human immunoglobulin G (IgG) (1:100, R&D Systems), monoclonal rabbit anti-human LRP-1 (1:100, Abcam, EPR3724, Cambridge, MA, USA), rabbit anti-human CypA (1:500, Abcam, ab42408), rabbit anti-human MMP-9 (1:500, Abcam, ab38898). antibodies, respectively.…”

“…8,8,29,31,33 Pericyte numbers were determined by counting the number of PDGFR -positive cell bodies on the abluminal side of the endothelial membrane (lectin) that colocalized with DAPI (4 0 ,6-diamidino-2-phenylindole)-positive nuclei using the ImageJ Cell Counter plug-in, as we and others previously described. 6,[31][32][33] The number of pericytes was expressed per mm 2 of tissue.…”

Microvascular Sprouting, Extension, and Creation of New Capillary Connections with Adaptation of the Neighboring Astrocytes in Adult Mouse Cortex under Chronic Hypoxia

“…Pericyte, which shares a common basement membrane with endothelial cells, has a crucial role in stabilizing the immature vessels, 37,38 and maintaining the functional integrity of the BBB. 39,40 Thus, pericyte-endothelial cell interactions must have a role in maintaining the BBB integrity and normalization of the vasculature during adaptation to chronic hypoxia. However, little is known about the involvement of the pericytes in the process of cerebral angiogenesis responding to hypoxia.…”

Nanoparticle transport across the blood brain barrier

“…Therefore, disrupted signaling between endothelial cells, pericytes and/or astrocytes may affect the integrity of the BBB. 9,13,28 In addition to regulating exchange of molecules between the peripheral blood circulation and the brain by its anatomical properties, the BBB is a metabolic barrier. A variety of degrading and metabolizing enzymes can be found at the membrane of brain capillary endothelial cells 6,32 along with a large number of transporter proteins that strictly regulate the influx and efflux of substances.…”