The Blood Brain Barrier In Health And Disease

Located at the interface between blood and the brain, the blood-brain barrier is a dynamic permeability barrier formed by a continuous layer of specialized endothelial cells endowed with important permeability, transport, and regulatory functions that both protect the internal milieu of the brain and allow essential nutrients to be transported into the brain. Over the last 25 years, we have witnessed remarkable expansion of our knowledge of the structure, biology, and function of the cerebral endothelium. In The Blood-Brain Barrier in Health and Disease, Volume 1, international experts discuss basic and new concepts and most recent advances pertaining to the development of the cerebral microvascular system. Subjects include the structure, function, permeability properties, transport mechanisms, and the inherent heterogeneity of the cerebral endothelium; the anatomy and physiological properties of the neurovascular unit; functional aspects of the choroid plexus; and important concepts and advances made over the last two decades that have shaped our understanding of the immunological function of the blood-brain barrier. This book is intended to serve as a valuable source of basic and advanced information for researchers, students, and clinicians interested in this fast-expanding field and stimulate further research well into the future.

The blood-brain barrier (BBB) is a complex and dynamic structure that protects the brain from cells within the vasculature, from the immune system and from pathogens. This barrier is present in arterioles, capillaries and venules and is formed at the level of adjacent endothelial cells, which are coupled to astrocytes, microglia, neurons and pericytes. The structure of this endothelial barrier is unique among endothelia of other organ systems and is composed of complexes made up of tight, gap and adherens junctions. In addition, it is the responsibility of the surrounding cellular elements to maintain the integrity of the junctional complexes and restrict the entry of substances from the blood into the brain. Changes in permeability of the BBB during physiologic and pathophysiologic conditions involve alterations in specific transporters at the level of the endothelium, activation of specific cellular second messenger pathways and/or the dissolution of the junctional complexes composing the BBB. This book focuses on various aspects that account for the formation and maintenance of the BBB, and on disease states that compromise this barrier.

Located at the interface between blood and the brain, the blood-brain barrier is a dynamic permeability barrier formed by a continuous layer of specialized endothelial cells endowed with important permeability, transport, and regulatory functions that both protect the internal milieu of the brain and allow essential nutrients to be transported into the brain. Abnormalities of the blood-brain barrier are increasingly recognized as a key component in the pathogenesis of a range of primary diseases of the brain and the secondary involvement of the brain from pathological processes in other organs. In The Blood-Brain Barrier in Health and Disease, Volume 2, international experts present comprehensive reviews and research accounts on blood-brain barrier dysfunction in infectious and inflammatory diseases, cerebrovascular diseases, stroke, trauma, vitamin deficiency, exposure to neurotoxicants, primary and metastatic brain tumors, and neurodegenerative diseases. This book is intended to serve as a guide and reference to basic and advanced information for researchers, students, and clinicians interested in this fast-expanding field and stimulate further research well into the future.

Located at the interface between blood and the brain, the blood-brain barrier is a dynamic permeability barrier formed by a continuous layer of specialized endothelial cells endowed with important permeability, transport, and regulatory functions that both protect the internal milieu of the brain and allow essential nutrients to be transported into the brain. Abnormalities of the blood-brain barrier are increasingly recognized as a key component in the pathogenesis of a range of primary diseases of the brain and the secondary involvement of the brain from pathological processes in other organs. In The Blood-Brain Barrier in Health and Disease, Volume 2, international experts present comprehensive reviews and research accounts on blood-brain barrier dysfunction in infectious and inflammatory diseases, cerebrovascular diseases, stroke, trauma, vitamin deficiency, exposure to neurotoxicants, primary and metastatic brain tumors, and neurodegenerative diseases. This book is intended to serve as a guide and reference to basic and advanced information for researchers, students, and clinicians interested in this fast-expanding field and stimulate further research well into the future.

This book is devoted to exploring the complexities of the blood-brain barrier. The book begins by reviewing the historical experiments that led to the concept of a barrier protecting the brain from variations in the blood. Transport kinetics and carrier-mediated processes are described, and the mechanism by which molecules can cross the barrier is discussed. Ways in which the barrier can be disrupted and opened are covered as well. Subsequent chapters in the book describe the transport of glucose and amino acids into the central nervous systems, cover recent findings by which peptides and proteins are able to gain entry or are excluded from the brain, and analyze models that can be used for investigating how the blood-brain barrier can be disordered in neurological disease processes.

Blood–brain barrier (BBB) breakdown leading to cerebral edema occurs in many brain diseases—such as trauma, stroke, inflammation, infection, and tumors—and is an important factor in the mortality arising from these con- tions. Despite the importance of the BBB in the pathogenesis of these diseases, the molecular mechanisms occurring at the BBB are not completely und- stood. In the last decade a number of molecules have been identified not only in endothelial cells, but also in astrocytes, pericytes, and the perivascular cells that interact with endothelium to maintain cerebral homeostasis. However, the precise cellular interactions at a molecular level in steady states and d- eases have still to be determined. The introduction of new research techniques during the last decade or so provide an opportunity to study the molecular mec- nisms occurring at the BBB in diseases. The Blood–Brain Barrier: Biology and Research Protocols provides the reader with details of selected morphologic, permeability, transport, in vitro, and molecular techniques for BBB studies, all written by experts in the field. Each part is preceded by a review that emphasizes the advantages and pitfalls of particular techniques, as well as offering much relevant current information. The techniques provided will be helpful to both beginners in BBB research and those more experienced investigators who wish to add a specific technique to those already available in their laboratories.

Despite the fact that the breakdown of the blood-brain barrier occurs in many brain diseases and is an important factor in mortality, the molecular mechanisms involved in the breakdown are not completely understood. In The Blood-Brain Barrier: Biology and Research Protocols, leading researchers and clinician-scientists present state-of-the-art morphologic, permeability, transport, in vitro, and molecular techniques to study the workings of the blood-brain barrier in health and disease. Described in step-by-step detail, each proven method includes an explanation of the theoretical basis of the method, a discussion of its advantages and limitations, notes on avoiding pitfalls, and examples of results obtained using the technique. At the cutting edge are techniques to explore the genomics and proteomics of brain endothelium. Comprehensive and state-of-the-art, The Blood-Brain Barrier: Biology and Research Protocols offers pharmacologists, physiologists, neuroscientists, neurosurgeons, and neurologists an array of powerful tools to isolate undiscovered molecules, deepen our understanding of their role in health and disease, and identify targets for future gene therapy and therapeutic intervention.