SWISS MEDICINE: BLOOD-BRAIN BARRIER

Breaking and building the wall: The biology of the blood-brain barrier in health and disease 21/11/2013 Blood-brain-barrier The blood-brain barrier (BBB) is a complex feature of brain endothelial cells that restricts the passage of blood-borne molecules into the brain parenchyma, while ensuring the delivery of essential nutrients and selected biomolecules. Brain vasculature is anatomically distinct from that of other organs and comprises endothelial cells, pericytes and astrocytes, which collectively form the neurovascular unit (NVU). This review provides a brief overview of the cellular components of the NVU and BBB characteristics. In addition, the regulation of brain vasculature by peripheral factors such as diet and systemic disease is discussed. Abstract Proper functioning of the brain vasculature is critical for the maintenance of optimal brain function. Brain ­parenchyma is separated from blood within the cerebral vasculature by the blood-brain barrier (BBB). The BBB is a collective term for brain-specific, endothelial cell characteristics that restrict the passage into the brain of blood-borne molecules that ensure delivery of essential nutrients and selected biomolecules. The principal ­features of the vertebrate BBB are closed cell-cell junctions, a low rate of transcytosis, the expression of various solute carriers and ATP-binding cassette transporters. In addition, blood vessels in the brain are anatomically distinct. The capillary bed of brain vasculature has full longitudinal coverage by pericyte processes. Furthermore, brain vasculature is covered by glial processes, the so-called astrocyte end-feet. The term neuro­vascular unit (NVU) is often used to describe brain blood vessels in order to underline the intimate physical and functional connection between the brain tissue and blood vessels. Another special feature of brain vessels is that they are immunologically quiescent. Specifically, the expression of leucocyte-adhesion molecules is low and few peripheral leucocytes enter into the brain parenchyma. The development and maturation of the BBB and NVU is directed by signals from the surrounding neural tissue and cells forming the NVU. The formation of BBB ­specific cell-cell junctions and expression of trans­porters for glucose and biomolecules on endothelial cells is induced by the neuroepithelium, whereas pericytes regulate the low transcytosis rate of brain ­endothelium. Astrocytes have merged as regulators of BBB immune quiescence and brain water transport. Endothelial cell-cell junctions, the most intensively studied component of the BBB, are composed of adherens and tight junctions, which are established by transmembrane proteins mediating homophilic extracellular interaction. The brain endothelium is equipped with a transport system that provides a selective route for nutrients, ions and bioactive macromolecules, and ensures elimination of toxic molecules. These transporters are expressed in a polarised manner that allows the effective exchange of molecules and ions between blood and the brain parenchyma. The list of CNS pathologies (e.g. leucoencephalopathies, arteriopathies, brain calcifications) caused by the ­dysfunction of cellular and acellular components of the NVU is long. In addition, BBB breakdown is associated with common neurodegenerative diseases such as ­Alzheimer’s and Parkinson’s diseases). Pathological changes in the BBB also occur in the setting of peripheral ­diseases, e.g., acute liver failure and hypoxic conditions such as cardiac arrest. A detailed mechanistic understanding of BBB alterations in these conditions is lacking. Even less well understood is how the BBB is maintained and regulated in the healthy organism. The molecular development and regulation of the BBB is currently under intense investigation. Clearly, a collective effort from research groups working in different fields (vascular biologists, physiologists, neurobiologists etc.) is needed to better understand the development and homeostasis of complex structures such as the BBB and NVU. Although the brain vascular development and deregulation during pathological conditions is better understood at the molecular and cellular level, the majority of specific questions remain unanswered. This is a summary of an open access article on www.smw.ch. Must be cited as: Keller A. Breaking and building the wall: the biology of the blood-brain barrier in health and disease. Swiss Med Wkly. 2013,143:w13892. - See more at: http://blog.smw.ch/breaking-and-building-the-wall-the-biology-of-the-blood-brain-barrier-in-health-and-disease/#sthash.Y8ejfNBj.dpuf