4.7 Article

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

Journal

CNS NEUROSCIENCE & THERAPEUTICS
Volume 27, Issue 1, Pages 36-47

Publisher

WILEY
DOI: 10.1111/cns.13569

Keywords

blood– brain barrier; central nervous system; inflammation; inflammatory factors; molecular mechanism

Funding

  1. National Natural Science Foundation of China [81771293]
  2. Science and Technology Innovation Commission of Shenzhen Municipality [JCYJ20170413165705083, JCYJ20200109114608075, SGLH20180625142404672]
  3. International collaboration project of Chinese Academy of Sciences [172644KYSB20200045]
  4. CAS-Croucher Funding Scheme for Joint Laboratories
  5. Guangdong Innovation Platform of Translational Research for Cerebrovascular Diseases
  6. Chinese Government Scholarship (CSC)

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The blood-brain barrier is a crucial physiological barrier that separates the central nervous system from the peripheral circulation. Disruption of the BBB by peripheral inflammation can lead to various CNS diseases.
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.

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