The Physiological Characteristics and Transcytosis Mechanisms of the Blood-Brain Barrier (BBB)

Elizabeth      CM de Lange

Abstract

The blood-brain barrier (BBB) is the vessel wall made up of specialized capillary endothelial cells, surrounded by astroglial endfeet and neurons, that govern the exchange of compounds between blood and brain. It protects the brain from harmful compounds potentially present in blood, while it is specifically designed to supply the brain with the required nutrients and to get rid of waste products. The BBB is structurally different from blood capillaries in other tissues. The BBB strictly limits the paracellular exchange of compounds by the so-called tight junctions. Moreover, the capillary endothelial cells contain metabolic enzymes that may convert a compound before entering the brain while transcellular passage across the BBB may be limited or increased by active transport systems. Thus the BBB has an important role in the relationship of the concentration-time profile of compounds in blood and those in the brain. The functionality of the BBB is dynamically regulated, depending on the given conditions. Important examples are changes in BBB functionality that may result in or are brought about by (CNS) disease conditions. All together this indicates the importance of investigations on BBB functionality and resulting transport of compounds for the design and optimization of therapeutic regimens. Thus, BBB investigation is an ever growing and dynamic field studied by pharmacologists, neuroscientists, pathologists, physiologists, and clinical practitioners. This review deals with a general introduction on the physiological characteristics of the BBB, its different transport systems, with particular emphasis on supposed transcytosis mechanisms at the BBB. Specific and detailed information on drug delivery approaches aiming at transcytosis into the brain will be dealt with in other parts of this special issue.

Keywords: Blood-brain barrier, transcytosis, transport, endothelial cells, astroglial endfeet, physiological characteristics of the BBB, transport systems, brain tissue, luminal endothelial membrane, choroid plexus epithelium, blood vessels, endothelial cells, luminal endothelial membrane, Brain cerebral capillaries