Blood Brain Barrier In Physiology And Medicine

The endothelial cells of the cerebral vasculature constitute, together with perivascular elements (astrocytes, pcricytes, basement membrane), the blood-brain barrier (BBB), which strictly limits and specifically controls the exchanges between the blood and the cerebral extracellular spacc.The existence of such a physical, enzymatic, and active barrier isolating the central nervous system has broad physiological, biological, pharmacological, and patho logical consequences, most of which are not yet fully elucidated. The Cerebral Vascular Biology conference (CVB '95) was organized and held at the "Carre des Sciences" in Paris on July I 0-12, 1995. Like the CVB '92 conference held in Duluth, Minnesota, three years ago, the objectives were to provide a forum for presentation of the most recent progresses and to stimulate discussions in the ticld of the biology, physiology. and pathology of the blood-brain barrier. The Paris conference gathered more than !50 participants. including investigators in basic neuroscience, physicians. and stu dents, who actively contributed to the scientific program by their oral or poster presentations. This volume contains a collection of short articles that summarize most of the new data that were presented at the conference. Six thematic parts focus on physiological transports. drug delivery, multidrug resistance P-glycoprotein, signal transduction at the BBB. interactions between the immune system and the cerebral endothelial cells, and the blood-brain barrier-related pathologies in the central nervous system. In addition, two introductory articles present new insights in the rapidly evolving topics of cerebral angiogenesis and gene transfer to the brain.

The blood-brain barrier is still not completely understood and therefore the subject of fascinating study. How are endogenous substances transported through the blood-brain barrier? What are the known therapeutic and toxic agents? How are they transported across cerebral microvessels? The discussion of these and other questions with far-reaching consequences for all neuroscientists can be found in this volume. This authoritative and up-to-date review of the blood-brain barrier gives a proper understanding of the topic. The experimental principles, the results of very recent research, as well as the implications that experimental research has for clinical treatment are thoroughly covered. Information is given on: - new findings based on classical physiological and pharmacological techniques, - results obtained from brain capillaries in vitro and in culture, - results obtained from the new scanning techniques (PET and MRI), - the immunology of the blood-brain barrier, - trace metal transport, - the pathological breakdown of the barrier and - the modification of drugs to increase their entry into the brain. Here is a source of information that is invaluable to specialists concerned with basic research in the neurosciences, with the design of neuropharmacological agents, with the radiological diagnosis of cerebral pathology or with the treatment of cerebral lesions!

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

This text/reference uses 574 figures and illustrations to help explain the relationships between blood and the cerebrospinal fluid (CSF) and central nervous system (CNS). The authors focus on the interaction of these fluids and the relative importance of the transport mechanisms of hormones from blood to nervous tissue. Carrier-mediated transport of many neuroactive peptides is discussed. Special aspects of the blood-brain barrier are covered in detail. An entire chapter is devoted to the comparative physiology of the CSF and the brain barriers. Physiologists in all fields will have an interest in the updated theories covered in this book.

This e-book will review special features of the cerebral circulation and how they contribute to the physiology of the brain. It describes structural and functional properties of the cerebral circulation that are unique to the brain, an organ with high metabolic demands and the need for tight water and ion homeostasis. Autoregulation is pronounced in the brain, with myogenic, metabolic and neurogenic mechanisms contributing to maintain relatively constant blood flow during both increases and decreases in pressure. In addition, unlike peripheral organs where the majority of vascular resistance resides in small arteries and arterioles, large extracranial and intracranial arteries contribute significantly to vascular resistance in the brain. The prominent role of large arteries in cerebrovascular resistance helps maintain blood flow and protect downstream vessels during changes in perfusion pressure. The cerebral endothelium is also unique in that its barrier properties are in some way more like epithelium than endothelium in the periphery. The cerebral endothelium, known as the blood-brain barrier, has specialized tight junctions that do not allow ions to pass freely and has very low hydraulic conductivity and transcellular transport. This special configuration modifies Starling's forces in the brain microcirculation such that ions retained in the vascular lumen oppose water movement due to hydrostatic pressure. Tight water regulation is necessary in the brain because it has limited capacity for expansion within the skull. Increased intracranial pressure due to vasogenic edema can cause severe neurologic complications and death.

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.

The blood-brain barrier serves to protect the brain from toxic substances whilst simultaneously allowing access to essential nutrients and chemical signals. At the interface between brain and body, knowledge of the blood-brain barrier forms an essential component in the complete understanding of a large proportion of medical disciplines. Nevertheless, it seems that ignorance of both the biology of this important membrane and the methodology suitable for its investigation still remains an impediment to progress in many fields, including, for example, the development of new and efficacious neuropharmaceuticals, cerebrovascular disease, Alzheimer's disease, cerebral AIDS and brain tumours. This introduction for both researchers and clinicians across the medical sciences is intended to aid both those beginning work directly in this area and those wishing simply to be better informed when interpreting information where the blood-brain barrier may be involved. Advances in both methodology and biology are detailed in 50 chapters from international authorities.