Breaking the Barrier: The Role of Proinflammatory Cytokines in BBB Dysfunction

The BBB is created by a special system of brain microvascular endothelial cells (BMECs), pericytes (PCs), the capillary basement membrane, and the terminal branches ("end-feet") of astrocytes (ACs). The key function of the BBB is to protect the central nervous system (CNS) from potentially harmful/toxic substances in the bloodstream by selectively controlling the entry of cells and molecules, including nutrients and components of the immune system. The loss of BBB integrity in response to neuroinflammation, as manifested by an increase in permeability, depends predominantly on the activity of proinflammatory cytokines. However, the pathomechanism of structural and functional changes in the BBB under the influence of individual cytokines is still poorly understood. This review summarizes the current state of knowledge on this topic, which is important from both pathophysiological and therapeutic points of view. The structures and functions of all components of the BBB are reviewed, with emphasis given to differences between this and other locations of the circulatory system. The protein composition of the interendothelial tight junctions in the context of regulating BBB permeability is presented, as is the role of pericyte-BMEC interactions in the exchange of metabolites, ions, and nucleic acids. Finally, the documented actions of proinflammatory cytokines within the BBB are discussed.