Cellular and signalling mechanisms that regulate the blood-brain barrier

The blood-brain barrier (BBB) is a unique specialization of central nervous system (CNS) capillary endothelial cells that controls molecular traffic between the blood and the brain. In doing so, the BBB maintains a safe and homeostatic environment for proper neuronal function. The BBB restricts drug delivery to the CNS, while BBB defects contribute to neurodevelopmental and neurodegenerative disorders. In this Review, we discuss the distinct features of CNS capillary endothelial cells that form the BBB. Meanwhile, interactions between capillary endothelial cells and surrounding pericytes, astrocytes and with the extracellular matrix of the basement membrane, are crucial for BBB formation and maintenance. We examine how molecular regulators of capillary endothelial cells and signalling pathways that control cell-cell interactions render the BBB a dynamic and selective interface. We highlight emerging areas of BBB research, including heterogeneity of brain vascular permeability and technology development. Finally, we discuss how insights from BBB biology are shaping therapeutic strategies targeting the BBB.