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Neurovascular Unit: a Focus on Pericytes

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Abstract

The blood–brain barrier (BBB) is a highly specialized system that controls the exchanges between the blood and the central nervous system (CNS). This barrier shields the CNS from toxic substances in the blood and provides nutrients to CNS, thus playing an essential role in the maintenance of homeostasis. The anatomical basis of the BBB is formed by the endothelial cells of brain microvasculature, with elaborated tight and adherens junctions, which together with pericytes, the basement membrane, and astrocytes, as well as neurons, microglia and oligodendrocytes form the neurovascular unit. The interaction between all these components guarantees a proper environment for neural function and a restricted permeability and transport. Pericytes were initially reported by Rouget in 1873 and since then they have been recognized as an important component of the BBB, despite the difficulty of their identification. Diverse functions have been assigned to pericytes, including a role in BBB properties, hemostasis, and angiogenesis, as well as a contractile, immune, and phagocytic function. These cells are also seen like multipotent cells and so with a great potential for therapy. Here, we review the neurovascular unit composition and the interplay between the diverse components, addressing pericytes with a particular detail.

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Abbreviations

ABC:

ATP-binding cassette

α-SMA:

α-smooth muscle actin

Ang:

Angiopoietin

AJ:

Adherens junction

BBB:

Blood–brain barrier

BM:

Basement membrane

BMVEC:

Brain microvascular endothelial cell

CAM:

Cell adhesion molecule

CNS:

Central nervous system

ECM:

Extracellular matrix

EC:

Endothelial cell

ER:

Endoplasmic reticulum

GFAP:

Glial fibrillary acidic protein

GLUT-1:

Glucose transporter-1

ICAM-1:

Intercellular adhesion molecule-1

IL:

Interleukin

JAM:

Junctional adhesion molecule

MHC:

Major histocompatibility complex

MMP:

Matrix metalloproteinase

MRP:

Multidrug resistance-associated protein

NVU:

Neurovascular unit

OPC:

Oligodendrocyte precursor cell

PDGF-β:

Platelet-derived growth factor-β

P-gp:

P-glycoprotein

RGS-5:

G-protein signaling-5

TEER:

Transendothelial electrical resistance

TGF-β:

Transforming growth factor-β

TJ:

Tight junction

VCAM-1:

Vascular cell adhesion molecule-1

VEGF:

Vascular endothelial growth factor

VEGFR2:

Vascular endothelial growth factor receptor 2

ZO:

Zonula occludens

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Acknowledgments

This work was supported by PTDC/SAU-FCF/68819/2006 grant from Fundação para a Ciência e a Tecnologia (FCT), Lisbon, Portugal (to M. A. B.) and PEst-OE/SAU/UI4013/2011 (to iMed.UL). We thank our colleagues Rui Silva, Inês Palmela, Filipa Lourenço Cardoso, and Pedro Pereira for some of the photos presented in the figures. We also thank Szilvia Veszelka, Ágnes Kittel, and Mária A. Deli for sharing with us the material presented in Fig. 2.

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  1. Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal

    Inês Sá-Pereira, Dora Brites & Maria Alexandra Brito

  2. Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

    Dora Brites & Maria Alexandra Brito

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  1. Inês Sá-Pereira
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Correspondence to Maria Alexandra Brito.

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Sá-Pereira, I., Brites, D. & Brito, M.A. Neurovascular Unit: a Focus on Pericytes. Mol Neurobiol 45, 327–347 (2012). https://doi.org/10.1007/s12035-012-8244-2

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