1570-159X/09 $55.00+.00 ©2009 Bentham Science Publishers Ltd. Mechanisms of the Penetration of Blood-Borne Substances into the Brain

Abstract: The blood-brain barrier (BBB) impedes the influx of intravascular compounds from the blood to the brain. Few blood-borne macromolecules are transferred into the brain because vesicular transcytosis in the endothelial cells is consid-erably limited and the tight junction is located between the endothelial cells. At the first line of the BBB, the endothelial glycocalyx which is a negatively charged, surface coat of proteoglycans, and adsorbed plasma proteins, contributes to the vasculoprotective effects of the vessels wall and are involved in maintaining vascular permeability. In the endothelial cy-toplasm of cerebral capillaries, there is an asymmetrical array of metabolic enzymes such as alkaline phosphatase, acid phosphatase, 5’-nucleotidase, adenosine triphosphatase, and nucleoside diphosphatase and these enzymes contribute to in-activation of substrates. In addition, there are several types of influx or efflux transporters at the BBB, such as P-glycoprotein (P-gp), multidrug resistance associated protein, breast cancer resistance protein, organic anion transporters, organic cation transporters, organic cation transporter novel type transporters, and monocarboxylic acid transporters. P-gp, energy-dependent efflux transporter protein, is instrumental to the barrier function. Several findings recently reported in-dicate that endothelial P-gp contributes to efflux of undesirable substances such as -amyloid protein from the brain or periarterial interstitial fluid, while P-gp likely plays a crucial role in the genesis of multiple vascular abnormalities that ac-company hypertension. In this review, influx and efflux mechanisms of drugs at the BBB are also reviewed and how medicines pass the BBB to reach the brain parenchyma is discussed. Key Words: Blood-brain barrier, P-glycoprotein, tight junction. 1