chapter  7
26 Pages

- Blood–Brain Barrier and the Neural Vascular Unit

This chapter focuses on some recent discoveries regarding molecular driving forces for cerebral angio-and barriergenesis and the formation of the gliovascular complex, which comprises the structural and functional unit of the blood-brain barrier (BBB). Progress made in our understanding of the ontogeny of the BBB, its

7.1 Introduction .................................................................................................. 179 7.1.1 The Blood-Brain Barrier: An Evolutionary Perspective .................. 180 7.1.2 Barriergenesis and the Contribution of the

Neuroglial Surrounding .................................................................... 181 7.1.3 Molecular Cues for Angio-and Barriergenesis ................................ 182 7.1.4 Pericytes and Their Speci¡c Role in BBB Development ................. 184 7.1.5 Molecular Anatomy of the Blood-Brain Barrier ............................. 185

7.2 Types of Cell Junctions at the Blood-Brain Barrier ..................................... 188 7.2.1 Adhesive Junctions ........................................................................... 189 7.2.2 Tight Junctions .................................................................................. 190 7.2.3 Gap Junctions .................................................................................... 191

7.3 Polarization at the BBB-Glial Interface ....................................................... 193 7.3.1 Disruption of the Gliovascular Interface in Pathologies .................. 193 7.3.2 Pathogens Breach of Blood-Brain Barrier ....................................... 194

7.4 Structure and Plasticity of Neurovascular Blood Flow ................................ 195 7.4.1 Gliovascular Interaction and Cerebral Hemodynamics .................... 195

7.5 Conclusions ................................................................................................... 198 References .............................................................................................................. 198

regulation, and interaction with the brain parenchyma in the adult brain is amazing and will certainly be helpful in approaching new strategies to treat a variety of human diseases of the brain in the future. Since numerous reviews, handbooks, and monographs dealing with the blood-brain barrier have been published (e.g., Dermietzel et al. 2006) within recent years, we primarily emphasize discoveries that are not of common knowledge and which in some way mark turnarounds in our former understanding of the BBB establishment and function. We start with a brief appraisal on the evolution of the BBB and continue with respect to molecular clues that drive the maturation of the BBB during ontogenesis. A focus is placed on the driving force of oxygen tension for angiogenesis and barriergenesis, which features the most characteristic aspect of the brain vasculature. This is followed by discussion of the impact of two cellular entities, neuroglial cells and pericytes, on the development and maintenance of the BBB. Two features of the BBB are of particular interest: the tight junction, which enables the cerebral endothelium to perform its barrier function, and the intimate association of the vasculature with the polarized astroglia. The formation of the glial endfeet has long been a descriptive term in histology. The discovery that these endfeet constitute highly differentiated plasmalemmal domains furnished with a complement of channels and regulatory, membrane-associated proteins that provide key features attributing to mechanisms responsible for brain homeostasis is a hallmark in BBB research. Finally, we give a brief account of some pathological aspects of the BBB and its underlying molecular mechanisms before this chapter ¡nishes, with some recent, in part controversial, aspects of the dynamics of vascular perfusion of brain tissue.