The blood-brain barrier

Abstract

Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Figures

Figure 1.

Components of the BBB. (A) Vascular cast of a spinal cord showing density of the CNS vascular network. (B) Electron micrograph (EM) of a cross section of a CNS vessel depicting a relationship among endothelial cells (ECs), pericytes (PCs), and astrocytes. (C) Magnified EM of ECs depicting a relationship among ECs (with tight junctions [TJ]), PCs, basement membranes (BMs), and astrocyte endfeet (AE). (D) Schematic representation of the cell types within the neurovascular unit. (E) Immunofluorescence micrograph depicting relationship of PCs (red) with ECs (green). (F) Micrograph depicting relationship of astrocytes (red-labeled with GFAP-cre; Rosa-tdTomato) with blood vessels (unstained). Astrocytes extend processes that ensheath the blood vessels, such that the outline of the blood vessels can be visualized by the endfeet of these processes (courtesy of Matthew Boisvert and Nicola Allen).

Figure 2.

Schematic representation of molecules of the BBB. CNS, central nervous system; VEcad, VE cadherin.

Figure 3.

Schematic representation of signaling regulating the blood–brain barrier in health and disease. ICAM, intercellular adhesion molecule; MMP, matrix metalloproteinase; ROS, reactive oxygen species.