The Blood-Brain Barrier and Its Microenvironment: Basic Physiology to Neurological Disease PDF

Preface

The cerebral capillaries are organized in a way that they form a continuous cellular barrier that isolates the brain from the systemic circulation. By its unique properties, the blood-brain barrier (BBB) restricts the entrance of blood-borne large and hydrophilic compounds into the brain, controls the supply of nutrients to the brain and restricts immune cell entry within the CNS. The inner biochemical and immunological environment of the CNS is thus closely regulated by the BBB. This phenomenon is largely due to the intrinsic nature of the cerebral vasculature, which differs in a number of properties from other non-CNS vascular beds, as well as to the unique cellular and molecular environment surrounding the BBB-endothelial cells.

The blood-brain barrier has now been acknowledged as a neuronal component of the central nervous system and actively regulates brain homeostasis by its specialized nature. It is only recently recognized that the dynamics of the blood-brain barrier are of crucial importance in the development of various neuro-pathological conditions. In this book, experts in the field address the latest advances in both the cellular and molecular biology of this highly specialized structure and discuss its functional characteristics under pathological conditions.

This book is divided in two sections; in the first section, the role and structure of the blood-brain barrier are addressed. In Chapter 1, Stefan Liebner and Britta Engelhardt describe the development of the blood-brain barrier and what special features are formed at the barrier during embryogenesis and in the neonatal period. Ultrastructural alterations at the level of the tight junctions during development will be elucidated. In chapter 2, Eric Shusta gives insight into the specialized nature of the brain endothelial features by discussing differences between peripheral and cerebral endothelium by the use of genomics and proteomics, allowing the identification of brain endothelial specific genes and proteins. In Chapter 3, Gijs Kooij, Jack van Horssen and Elga de Vries provide a detailed description on the protein composition of the tight junction and describe in detail how the junction is regulated by a number of signalling molecules. In Chapter 4, Eric Ronken and Guus van Scharrenburg present their view on how trophic factors may influence the blood-brain barrier and discuss potential therapeutic strategies to modulate barrier permeability. Lars Edvinsson describes the neuronal influence on the blood-brain barrier in Chapter 5 and offer information on how various neuronal pathways affect the dynamics of the barrier and vice versa. Since the BBB has the capacity to actively regulate the passage of solutes and drugs from the brain-to-blood and blood-to-brain direction, pharmacologists are searching for ways to allow drugs to enter the CNS by facilitating their transport across the BBB. In Chapter 6, Wandong Zhang and Danica Stanimirovic describe in detail the various transport systems that exists at the BBB and how these influence the transport of compounds across the BBB. In Chapter 7, Be´atrice Heurtault and Jean-Pierre Benoit address the potentials of the use of liposomes and other non-viral vectors and the described transport mechanisms for the delivery of drugs through the BBB to the CNS.

In section II, we have decided to present the current knowledge on CNS-directed inflammatory diseases and other neuropathological conditions that either affect the BBB or are a consequence of BBB dysfunction. In Chapter 8, Jack Antel, Katarzyna Biernacki and Alexandre Prat discuss whether brain endothelial cells themselves have a role in the inflammatory response and debate whether brain endothelial cells can function as antigen presenting cells. In Chapter 9, Zsuzsana Fabry and co-workers present the various mediators involved in the process of T lymphocyte infiltration into the CNS. Additionally, John Greenwood, David Wateridge and Patric Turowski describe the dynamic role of the brain endothelium in cellular migration in Chapter 10 and address how adhesion molecules actively participate in this process by initiating signal transduction events. In Chapter 11, Alexandre Prat and Elga de Vries introduce the molecular mechanisms of monocyte migration across the brain endothelium and discuss how these cells are of importance in the development of new lesion during the chronic neuro-inflammatory disease multiple sclerosis. Babs Fabriek, Ian Galea, Hugh Perry and Christine Dijkstra discuss the role of a relatively new cell type of the blood-brain barrier, the perivascular macrophage, in the neuro-inflammatory response in Chapter 12. The role of inflammatory mediators in controlling blood-brain barrier permeability and cellular migration are discussed in Chapter 13 by Melissa Callahan and Richard Ransohoff, who address the role of the family of the chemo-attractant chemokines and by Gary Rosenberg who shares his view on how the family of the matrix metalloproteinases and other proteolytic enzymes influence BBB permeability. Hartwig Wolburg and Arne Warth describe in Chapter 15 the interplay of the brain endothelium and its neighbouring cells, in particular astrocytes. In Chapter 16 Melissa Fleegal, Sharon Horn and Thomas Davis describe the effect of stroke on the BBB and the role of the BBB on post-anoxic CNS damage. Monique Mulder and Raj Kalaria in Chapter 17 describe the role of apolipoproteins in controlling barrier permeability, which is a class of proteins that so far has not been taken into consideration in terms of influence to barrier properties. Not only stroke and multiple sclerosis influence BBB permeability, severe alterations in the barrier properties are also observed after brain trauma as discussed in Chapter 18 by Maria Cristina Morganti-Kossmann and co-workers. Elegant imaging techniques have revealed that the blood brain permeability may be altered in time under neuro-inflammatory conditions. In Chapter 19, Erwin Blezer describes the use of various imaging techniques to monitor BBB permeability in vivo. In the last chapter, Natalie Arbour will elucidate the mechanisms of non- HIV viral entry into the central nervous system through interaction with the brain endothelium.

This new and exciting book provides a complete overview of the dynamics of the blood-brain barrier. We hope to stimulate both clinicians and researchers to look upon the BBB as an active player in a number of physiological and pathological conditions affecting the CNS. The contributors have done an excellent job in making their chapters of high scientific merit by presenting their latest results and sharing their hypotheses and we firmly believe that this will open new avenues of collaboration for BBB research.