Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms

Abstract

The blood-brain barrier (BBB) is an important physiological barrier that separates the central nervous system (CNS) from the peripheral circulation, which contains inflammatory mediators and immune cells. The BBB regulates cellular and molecular exchange between the blood vessels and brain parenchyma. Normal functioning of the BBB is crucial for the homeostasis and proper function of the brain. It has been demonstrated that peripheral inflammation can disrupt the BBB by various pathways, resulting in different CNS diseases. Recently, clinical research also showed CNS complications following SARS-CoV-2 infection and chimeric antigen receptor (CAR)-T cell therapy, which both lead to a cytokine storm in the circulation. Therefore, elucidation of the mechanisms underlying the BBB disruption induced by peripheral inflammation will provide an important basis for protecting the CNS in the context of exacerbated peripheral inflammatory diseases. In the present review, we first summarize the physiological properties of the BBB that makes the CNS an immune-privileged organ. We then discuss the relevance of peripheral inflammation-induced BBB disruption to various CNS diseases. Finally, we elaborate various factors and mechanisms of peripheral inflammation that disrupt the BBB.

Keywords: blood-brain barrier; central nervous system; inflammation; inflammatory factors; molecular mechanism.

FIGURE 1

Schematic diagram of the physiological characteristics of the BBB. GLUT1, glucose transporter 1; LAMs, leukocyte adhesion molecules

FIGURE 2

Mechanisms of BBB disruption induced by peripheral inflammation. 1 Changes in tight junctions; 2 damage to endothelial cells; 3 activation of astrocytes and microglia; 4 alteration of multiple transport pathways and receptors; 5 penetration of peripheral immune cells