The blood-brain barrier (BBB) is composed of specialized brain endothelial cells (BECs) that are surrounded by pericytes, astrocytes, and neurons. These neurovascular units form intracellular tight junctions between BECs, which limit the passive diffusion of molecules into the CNS. BECs are enriched with nutrient transporters, such as glucose transporters, amino acid transporters, and fatty acid transporters, for efficient uptake into the brain from the blood. On the other hand, the enrichment of polarized efflux transporters, such as P-glycoprotein (PGP), breast cancer resistance protein (BCRP), and multidrug resistance-associated proteins (MRPs) in BECs protects the brain from toxic factors and pathogens. Because of drug efflux by the BBB, the delivery of therapeutic drugs into the brain to treat CNS diseases has been a major challenge. The BBB is also associated with brain disease, as its impairment correlates with neurodegenerative diseases including Alzheimer's disease and Parkinson's disease (Desai et al., 2007, Saito and Ihara, 2014). These reasons have spurred researchers to establish a BBB model for analyzing the dysfunction of neurovascular units and drug permeability in vitro.
