Alterations in Blood‒brain Barrier (BBB) Integrity Related to Proinflammatory Cytokines

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. 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 (leakage), occurs with the dominant participation 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 clinical–therapeutic points of view. The structures and functions of all components of the BBB are discussed, with particular attention given to the phenotypic differences between BMECs and the vascular endothelium in 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 summarized.