Physiology of the CSF and Blood-Brain Barriers


Book Description

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.




The Blood-Cerebrospinal Fluid Barrier


Book Description

Despite the existence of two barrier systems in the brain, research over the last century has mostly focused on the blood-brain barrier rather than on the blood-CSF barrier. Today, there is a greater understanding of the function of the blood-CSF barrier and of the choroid plexus, a tissue that is the primary site of this barrier. With the growing number of studies that focus on the role of the blood-CSF barrier in CNS homeostasis and neurological disorders, a modern overview of the blood-CSF barrier is long overdue. The Blood-Cerebrospinal Fluid Barrier is exclusively devoted to the blood-CSF barrier. Internationally renowned experts discuss the most recent progress in the field of choroid plexus physiology and update our knowledge of the function of the blood-CSF barrier. The book begins with an overview of the development and morphology of the choroid plexus, and then covers various aspects of its function, such as the regulation of choroidal blood flow, ion transport, and the production and transport of polypeptides. Following an extensive section on the role of the choroid plexus in CNS disorders, the final section discusses in vitro, in vivo, and in situ models of the blood-CSF barrier. This unique book analyzes a wealth of new research on the proven and potential roles of the choroid plexus/blood-CSF barrier in the brain. It is a valuable resource that will foster future studies in neuroscience, pharmacology, and toxicology.




The Cerebral Circulation


Book Description

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.




Physiology of the CSF and Blood Brain Barriers


Book Description

The cerebrospinal fluid (CSF) is a clear colorless fluid found in the brain and the spinal cord. It acts as a cushion for the brain, providing basic immunological and mechanical protection to the brain inside the skull. It serves an important role in cerebral autoregulation of cerebral blood flow. The brain produces approximately 500 ml of cerebrospinal fluid everyday. The blood brain barrier (BBB) is a selective semipermeable boundary separating the circulating blood from the brain and the extracellular fluid of the central nervous system. It restricts the diffusion of solutes in the blood and hydrophilic molecules into the CSF but allows the diffusion of hormones, oxygen, carbon dioxide and other polar molecules. The blood brain barrier acts to protect the brain from circulating pathogens. In cases where an infection occurs, a drug has to be administered directly into the CSF such that it can cross over into the blood-cerebrospinal fluid barrier. This book contains some path-breaking studies in the physiology of the cerebrospinal fluid and blood brain barriers. It will also provide interesting topics for research, which interested readers can take up. Coherent flow of topics, student-friendly language and extensive use of examples make this book an invaluable source of knowledge.




Physiology and Pharmacology of the Blood-Brain Barrier


Book Description

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!




Magnesium in the Central Nervous System


Book Description

The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.




The Blood Brain Barrier (BBB)


Book Description

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.




Cerebrospinal Fluid in Clinical Neurology


Book Description

The cerebrospinal fluid (CSF) is an invaluable diagnostic tool in clinical neurology, not only in the evaluation of inflammatory, degenerative, and malignant diseases of the nervous system, but also in the diagnosis of all forms of cerebral and subarachnoidal bleedings. The CSF can be easily obtained by lumbar puncture and a set of basic analyses can be conducted using relatively simple laboratory methods. By combining different CSF parameters, a wide range of diagnostic entities can be identified. However, properly interpreting the test results requires a high level of expertise and cannot be achieved by just reporting on individual analytic values. This book covers essential aspects of cerebrospinal fluid analysis and its use in the diagnosis of common neurological diseases. The first part addresses preclinical aspects such as the history of CSF, as well as the anatomical, physiological, and biological background of this valuable fluid. In addition, CSF collection, its preanalytical and methodological implications, and the increasing number of disease-specific markers in CSF are discussed in detail. Lastly, CSF analyses are put into context with clinical syndromes, demonstrating their diagnostic value in neurological clinical practice. Cerebrospinal Fluid in Clinical Neurology helps readers understand the preanalytical and analytical aspects of CSF diagnostics and offers a valuable reference guide for interpreting CSF results during the clinical work-up for neurological patients.




The Cerebral Microvasculature


Book Description

As traced by Uichael Bradbury in his recently published monograph, The Concept of a BZood-Brain Barrier, the idea of a scientific challenge is just about as old as the twentieth century. Curiously, it remains undefined. Is it a structure or structures as some use the term, or is it a reciprocal per meability, a force-flow relationship, as do others, or is it a group of processes, some more specialized than others? Depend ing upon the observer, the method, and what is observed, it seems to be each of these or all. This Symposium takes as its focus of interest the micro vasculature of the brain and includes considerations of blood flow, the properties of vessel walls and the control of flow and permeability. In addition perturbations that change the characteristics of the flow of materials are given attention. By changing the usual focus of interest, the organizers, Drs. Suddith and Eisenberg, have given a fresh outlook to the subject and now, by publication of the Proceedings, have arranged for wide availability of these interesting papers. Keasley Welch v PREFACE A symposium on the cerebral microvasculature and its function in the blood-brain barrier was held at The University of Texas Medical Branch, Galveston, in the summer of 1979. Investigators from the United States and Europe met to discuss their recent work.




Drug Delivery to the Brain


Book Description

The development of new CNS drugs is notoriously difficult. Drugs must reach CNS target sites for action and these sites are protected by a number of barriers, the most important being the blood –brain barrier (BBB). Many factors are therefore critical to consider for CNS drug delivery, e.g. active/passive transport across the BBB, intra-brain distribution, and central/systemic pharmacokinetics, to name a few. Neurological disease and trauma conditions add further complexity because CNS barriers, drug distribution and pharmacokinetics are dynamic and often changed by disease/trauma. Knowledge of all these factors and their interplay in different conditions is of utmost importance for proper CNS drug development and disease treatment. In recent years much information has become available for a better understanding of the many factors important for CNS drug delivery and how they interact to affect drug action. This book describes small and large drug delivery to the brain with an emphasis on the physiology of the BBB and the principles and concepts for drug delivery across the BBB and distribution within the brain. It contains methods descriptions for studying drug delivery, routes and approaches of administering drugs into the brain, the influence of disease, and drug industry perspectives. Therewith, it contributes to an in-depth understanding of the interplay between brain (patho)-physiology and drug characteristics. Furthermore, the content is designed to be both cutting-edge and educational, so that the book can be used in high-level training of academic and industry scientists with full references to original publications. ​