The Blood-brain-barrier (BBB) provides both anatomical and physiological protection for the central nervous system (CNS), shielding the brain for toxic substances in the blood, supplying brain tissues with nutrients and filtering harmful compounds from the brain back to the bloodstream. The BBB is composed of four main cellular elements: endothelial cells (ECs), astrocyte end-feet, microglial cells, and pericytes. Transport across the BBB is limited by both physical and metabolic barriers (enzymes, and different transport systems). Tight junctions (TJs) present between ECs form an important barrier against diffusion, excluding most blood-borne substances for entering the brain.