Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences

A constant and well-controlled composition of the extracellular fluid in the central nervous system (CNS) is essential for efficient neuronal processing. Invertebrate nervous systems, which are far less complex than the mammalian brain, are protected from fluctuations in composition of body fluids by a barrier that is formed by glial cells and this arrangement also applies to some ancestral vertebrates. With the CNS becoming more complex during evolution, an endothelial barrier appeared, giving a strong selective advantage. Consequently, all existing vertebrates, except for a few fish species, have endothelial blood-brain barriers (BBB).The BBB and the blood-cerebrospinal fluid barrier (BCSFB) are formed by brain endothelial cells (BECs) and choroid plexus (CP) epithelial cells, respectively. The BBB and the BCSFB are not only anatomical barriers, but also dynamic tissues that express multiple transporters, receptors and enzymes. Brain capillaries are closely associated with perivascular astrocytic end-feet, pericytes and microglia that influence BBB permeability and, together with brain endothelial cells, constitute a "neurovascular unit".The two main functions of these barriers are to impede free diffusion between brain fluids and blood and to provide transport processes for essential nutrients, ions and metabolic waste products. Hence, the aim of this review is to address similarities and differences in the molecular biology of cellular junctions, solute carrier transporters, ATP-binding cassette transporters and ion transporters at the BBB and the BCSFB.Although there are several similar features between the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), it should be kept in mind that the cellular basis of these two structures as well as their primary functions differ: BBB is located in brain capillaries and, thus, it is an endothelial structure with its main role to protect the brain from physiological fluctuations in plasma concen