The Blood Cerebrospinal Fluid Barrier

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.

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.

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.

Understanding the structure and function of the blood-brain barrier (BBB) and recogniz ing its clinical relevance require a concert of scientific disciplines applied from a view point of integrative physiology rather than from only molecular or analytical approaches. It is this broad scope that is emphasized in this book. In my opinion, four original contributions define the field as it exists today. The first, a monograph by Broman,1 entitled The Permeability of the Cerebrospinal Vessels in Normal and Pathological Conditions, was the model for many subsequent clinical and 3 experimental studies on BBB pathology. Second, experiments by Davson, summarized in his book entitled Physiology of the Ocular and Cerebrospinal Fluids, indicated that passive entry of nonelectrolytes into brain from blood is governed largely by their lipid 4 solubility. This research supported the original suggestion by Gesell and Hertzman that cerebral membranes have the semipermeability properties of cell membranes. The modem era of the barrier was introduced with the 1965 paper by Crone,2 entitled "Facilitated transfer of glucose from blood to brain tissue. " This paper identified stereospecific, facilitated transport of glucose as part of a system of regulatory barrier properties at a time when only a barrier to passive diffusion had been contemplated. Finally, the 1967 paper by Reese and Kamovsky, 11 entitled "Fine structural localization of a blood-brain barrier to exogenous peroxidase," sited the barrier at the continuous layer of cerebrovascular endothelial cells, which are connected by tight junctions.

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.

This PIR volume presents a comprehensive collection of reviews that focus on the role of the blood-brain barrier (BBB) during steady-state and inflamed conditions. Within the central nervous system (CNS) the constantly changing bloodstream is strictly separated from the CNS parenchyma by the BBB. However, viruses, bacteria, parasites and auto-aggressive immune cells can penetrate the barrier and significantly contribute to CNS inflammation. The BBB can actively contribute to neuroinflammation by presentation of chemokines, expression of cell adhesion molecules and alterations of barrier properties. As such, understanding the role of the BBB under healthy and pathological conditions is essential to the development of new drugs to efficiently combat inflammatory diseases of the CNS.

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-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.