Figure 1.

Schematic representation of the blood–brain barrier and active transport mechanisms. The blood–brain barrier (BBB) is formed by a monolayer of specialized endothelial cells, which form together with pericytes, astrocytes, and the basement membrane (BM) to create the neurovascular unit. The BM is a thin sheet of supporting extracellular matrix, including fibronectin, and is composed of endothelial BM and the astrocyte-derived parenchymal BM. Endothelial cells are tightly connected via tight and adherens junctions, which prevent the paracellular passage of molecules. Active transport mechanisms across the BBB include receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT). RMT involves ligand–receptor binding, followed by endocytosis of the receptor complex, intracellular trafficking, and exocytosis at the basal membrane [114]. Conversely, cationic molecules can interact with the negatively charged membrane, thereby inducing transcellular transport of the positively charged molecule. See the text for more details. JAM—junction adhesion molecule; TJ—tight junction.