Fig. 3.

Pathways for molecular transport across the BBB. The cellular and molecular structure of the BBB makes this barrier highly restrictive and selective to molecules that can only cross the BBB through specific mechanisms. Small molecules like glucose are able to enter the brain using for example the glucose transporter Glut-1 as carrier in a Carrier-Mediated Transport. Small lipophilic molecules are able to overcome the BBB via passive diffusion in the Transcellular Lipophilic Pathway. Small hydrophilic molecules, unable to cross through the endothelial cells, are small enough to pass through the Tight Junctions into the brain parenchyma by the Paracellular Pathway. Some cationic molecules are able to interact with the negative charges on the surface of the endothelial cells and cross this barrier in a low capacity and non-specific mechanism called Adsorptive Transcytosis. Finally, large molecules, such as transferrin and insulin, enter the brain parenchyma via specific receptors expressed on the surface of endothelial cells in a mechanism called Receptor-Mediated Transcytosis