From Blood-to-Brain: Regulating the Permeability of the Blood-Brain Barrier

B.      Gomez-Gonzalez; K.      Sanchez-Alegria; J.      Velazquez-Moctezuma

Abstract

The blood-brain barrier is the structure that maintains central nervous system homeostasis; it is composed of brain endothelial cells, astroglia, pericytes, microglia, and of the extracellular matrix components basal lamina and glycocalyx. The blood-brain barrier constitutes the main interface between the brain and the periphery; therefore it is the main structure regulating the passage of molecules from blood-to-brain and vice versa. At brain endothelial cells are expressed numerous members of the solute carrier (SLC) and ATP-binding cassette (ABC) gene families; those carriers exert selective transport and preclude free exchange of molecules from blood-to-brain. In addition, brain endothelial cells present low paracellular diffusion and vesicle-mediated transport. The regulation of the blood-brain barrier permeability is essential to guarantee nutrient supply to brain cells, but also to allow selective passage of drugs designed to treat brain diseases. This review describes both the pharmacological and physiological approaches to modulate the permeability of the blood-brain barrier. Finally we propose that once more data on blood-brain barrier normal physiology are obtained, health professionals will be able to take advantage of normal variations in blood-brain barrier permeability to administer drugs aimed to affect the central nervous system in the critical time window of blood-brain barrier “opening”.

Keywords: blood-brain barrier permeability, brain endothelial cells, caveolae, receptor-mediated endocytosis, carrier systems, tight junctions, Beta-catenin, homotypically, paracellular leukocyte, lipophilic, neovascularization, abluminal, Plasminogen, diencephalon, dementia.