Pericytes regulate the blood–brain barrier

By A. Armulik, G. Genové, M. Mäe, Maya H. Nisancioglu, Elisabet Wallgard, C. Niaudet, Liqun He, J. Norlin, P. Lindblom, K. Strittmatter and 2 more. Nature, 2010

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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.

Subfields: Cell Biology, Neurology, Oncology

View Paper: https://www.semanticscholar.org/paper/f31de3641a9518b8bc20b75f36df0dd7bc7639b4

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Citations in the corpus

Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells (2017, background): “We considered that high concentrations of cytokines crossing the BBB might activate brain vascular pericytes, which together with ECs play an important role in maintenance of the BBB (16, 17).”
Fibroblasts in fibrosis: novel roles and mediators (2014, background): “Pericytes regulate the permeability of the blood vessel wall; for example, pericytes are the principal cell type that regulates the permeability of the blood–brain barrier (Armulik et al., 2010).”
Regional blood flow in the normal and ischemic brain is controlled by arteriolar smooth muscle cell contractility and not by capillary pericytes (2015, neutral): “These cells are thought to play important roles in microvascular development, angiogenesis (Armulik et al., 2010; Daneman et al., 2010), and maintenance of the blood brain barrier (Bell et al., 2010), and are implicated in a variety of neuropathological conditions (Bell et al., 2010; Hall et al.,…”
The blood–brain barrier in systemic infection and inflammation (2021, background): “Another is the platelet-derived growth factor receptor β (PDGFR-β), mutations in which cause Fahr’s disease [128]; the normal protein is essential for pericyte recruitment and maintenance at the BBB [59].”
Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation (2012, positive): “(a) The basal lamina protein agrin increases claudin-5 (Cld5) and occludin expression [92]; (b) Aquaporin-4 density, regulated by agrin, stabilizes TJ complexes through ZO-1 expression [93]; (c) β1-integrin engagement stabilizes Cld5 localization at the TJ [94]; (d) astrocyte/pericyte-secreted TGF-β”
The blood–brain barrier in health and disease: Important unanswered questions (2020, background): “Additionally, pericytes are important for BBB function throughout life (Armulik et al., 2010), suggesting that similar signals are required for BBB formation and maintenance.”
The blood–brain barrier: Structure, regulation and drug delivery (2023, background): “83 If the amounts of pericytes reduce, the tight junctions between endothelial cells will also be reduced.”