Research progress of mechanisms for tight junction damage on blood–brain barrier inflammation

Abstract

Inflammation in the central nervous system (CNS) contributes to disease pathologies by disrupting the integrity of the blood–brain barrier (BBB). Tight junctions (TJ) are a key component of the BBB. Following hypoxic–ischaemic or mechanical injury to the brain, inflammatory mediators are released such as cytokines, chemokines, and growth factors. Simultaneously, matrix metalloproteinases (MMPs) are released which can degrade TJ proteins. Subsequently, the function and morphology of the BBB are disrupted, which allows immune cells an opportunity to enter into the brain parenchyma. This review summarises the information on the role of TJ protein families in the BBB and provides a comprehensive summary of the mechanisms whereby inflammation breaks down the BBB by increasing degradation of TJ proteins.

Keywords:

• Blood–brain barrier
• tight junction
• inflammation
• tight junction proteins

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by National Major Scientific and Technological Special Project for “Significant New Drugs Development” during the Thirteenth Five-year Plan Period [No. 2016ZX09101031] and the “Double First-Class” Construction Technology Innovation Team Project of China Pharmaceutical University [Nos. CPU2018GY23 and CPU2018GY24] and China Pharmaceutical University “Double First-Class” Construction Graduate Education and Teaching Project (JGYB201909).