Humana Press Brain Homeostasis in Health and Disease Edited by Wolfgang Walz The Neuronal Environment The Neuronal Environment Contemporary Neuroscience The Neuronal Environment: Brain Homeostasis in Health and Disease, edited by Wolfgang Walz, 2002 Neurotransmitter Transporters: Structure, Function, and Regulation, 2/e, edited by Maarten E. A. Reith, 2002 Pathogenesis of Neurodegenerative Disorders, edited by Mark P. Mattson, 2001 Stem Cells and CNS Development, edited by Mahendra S. Rao, 2001 Neurobiology of Spinal Cord Injury, edited by Robert G. Kalb and Stephen M. Strittmatter, 2000 Cerebral Signal Transduction: From First to Fourth Messengers, edited by Maarten E. A. Reith, 2000 Central Nervous System Diseases: Innovative Animal Models from Lab to Clinic, edited by Dwaine F. Emerich, Reginald L. Dean, III, and Paul R. Sanberg, 2000 Mitochondrial Inhibitors and Neurodegenerative Disorders, edited by Paul R. Sanberg, Hitoo Nishino, and Cesario V. 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Production Editor: Diana Mezzina Cover Illustration: Figure 9 from Chapter 4, “Transmitter-Receptor Mismatches in Central Dopamine, Serotonin, and Neuropeptide Systems,” Further Evidence for Volume Transmission, by A. Jensson, L. Descarries, V. Cornea-Hébert, M. Riad, D. Vergé, M. Bancila, L. F. Agnati, and K. Fluxe. Cover design by Patricia Cleary. For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel.: 973-256-1699; Fax: 973-256-8341; E-mail: humana@humanapr.com; or visit our Website: www.humanapress.com. Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Humana Press Inc., provided that the base fee of US $10.00 per copy, plus US $00.25 per page, is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to Humana Press Inc. The fee code for users of the Transactional Report- ing Service is: [0-89603-882-3/02 $10.00 + $00.25]. Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 Library of Congress Cataloging in Publication Data The neuronal environment: brain homeostasis in health and diease/edited by Wolfgang Walz p. cm (Contemporary neuroscience) Includes bibliographical references and index. ISBN : 0-89603-882-3 (alk. paper) 1. Neurons Physiology. 2. Homeostasis. 3. Neuroglia. 4. Brain Metabolism. 5. Blood-brain barrier. I. Walz, Wolfgang. II. Series. QP363.N47758 2002 612.8’2 dc21 2001039827 Preface To function properly, neurons cannot tolerate fluctuations of their local environ- mental variables. This mainly results from their high degree of specialization in synap- tic integration and action potential conduction. Even small changes of certain extracellular ion concentrations, as well as in the dimensions of the extracellular space, alter ion channel kinetics in such a way as to distort the information represented by the nerve impulses. Another potential problem is the huge consumption of glucose and oxygen by neurons caused by the heavy compensatory ion pumping used for counter- acting passive ion flux. This problem is compounded by the low glucose storage capac- ity of the neurons. A complicated structure surrounds the neurons to sustain the required level of metabolites and to remove waste products. The Neuronal Environment: Brain Homeostasis in Health and Disease examines the function of all the components involved, including their perturbation dur- ing major disease states, and relates them to neuronal demands. The two introductory chapters focus on neuronal requirements. The dependence of their excitability on external factors that accumulate in the extracellular space, as well as their varying demands for energy metabolites, are described. Following that, the close interaction of neurons with elements of their microenvironment is illustrated. The extracellular space is no longer seen as a passive constituent of the CNS, but as a separate compartment in its own right, as a communication channel, and an entity that reacts with plastic changes in its size that will affect the concentrations of all its contents. Astrocytes participate in many neuronal processes, particularly in the removal of excess waste and signal sub- stances, the supply of energy metabolites, and the modulation of synaptic transmission. In addition to their homeostatic role, astrocytes are now seen as an active partner involved in synaptic transmission between neurons. The classical example of a close relationship of neurons with a component of their environment is, of course, their rela- tionship with the surrounding myelin sheath. This speeds up action potential conduc- tion, but is itself a potential source of problems in various disease states. In the last few years new imaging techniques have demonstrated a close coupling between local blood flow and neuronal activity, and several theories have been put forward to explain these interactions. The special status of the brain in having its own insulated circulation system—the cerebrospinal fluid contained in the ventricles and ducts—is also under- lined. The brain is the only organ that is protected from fluctuations of blood-borne chemicals by the existence of the blood–brain barrier. However, windows exist in this barrier in the form of the circumventricular organs that allow direct two-way commu- nication between neurons and blood constituents. Finally, despite their protection and insulation, the neurons are accessible to the immune system. Resident macrophages and invasion by blood-borne immune cells that cross the endothelial cell barrier enable v an immune reaction to take place. This complex interaction of neurons with their immediate environment is integral to the tasks that the neurons must perform to ensure that the organism can cope with its environmental challenges. Most diseases originat- ing in the brain start in these accessory systems of the neuronal microenvironment and affect neurons only second hand. Therefore, understanding the elements of the neu- ronal environment and the interactions with neurons, and with each other, is crucial in understanding the development and impact of most brain diseases. All the authors contributing to The Neuronal Environment: Brain Homeostasis in Health and Disease have made an attempt not only to explain the normal functioning of these accessory elements, but also their involvement in major diseases. Therefore, this book not only addresses researchers, graduate students, and educators who want to understand the complex environment of neurons, but also health professionals who need to know more about the normal homeostatic role of the neuronal environment to follow disease patterns. Wolfgang Walz vi Preface Contents vii Preface v Contributors ix I. NEURONAL ACTIVITY AND ITS DEPENDENCE ON THE MICROENVIRONMENT 1 Central Nervous System Microenvironment and Neuronal Excitability 3 Stephen Dombrowski, Imad Najm, and Damir Janigro 2 Neuronal Energy Requirements 25 Avital Schurr II. BRAIN MICROENVIRONMENT 3 Plasticity of the Extracellular Space 57 Eva Syková 4 Transmitter–Receptor Mismatches in Central Dopamine, Serotonin, and Neuropeptide Systems: Further Evidence for Volume Transmission 83 Anders Jansson, Laurent Descarries, Virginia Cornea-Hébert, Mustapha Riad, Daniel Vergé, Mircea Bancila, Luigi Francesco Agnati, and Kjell Fuxe 5 The Extracellular Matrix in Neural Development, Plasticity, and Regeneration 109 Jeremy Garwood, Nicolas Heck, Franck Rigato, and Andreas Faissner 6 Homeostatic Properties of Astrocytes 159 Wolfgang Walz and Bernhard H. J. Juurlink 7 Glutamate–Mediated Astrocyte–Neuron Communication in Brain Physiology and Pathology 187 Micaela Zonta and Giorgio Carmignoto 8 Axonal Conduction and Myelin 211 Jeffrey D. Kocsis 9 Coupling of Blood Flow to Neuronal Excitability 233 Albert Gjedde III. BRAIN MACROENVIRONMENT 10 Choroid Plexus and the Cerebrospinal–Interstitial Fluid System 261 Roy O. Weller viii Contents 11 The Blood–Brain Barrier 277 Richard F. Keep 12 Circumventricular Organs 309 James W. Anderson and Alastair V. Ferguson 13 Glial Linings of the Brain 341 Marc R. Del Bigio IV. I MMUNE SYSTEM-NEURON INTERACTIONS 14 Microglia in the CNS 379 Sophie Chabot and V. Wee Yong 15 Invasion of Ischemic Brain by Immune Cells 401 Hiroyuki Kato and Takanori Oikawa Index 419 Contributors LUIGI FRANCESCO AGNATI, Department of Human Physiology, University of Modena, Modena, Italy JAMES W. ANDERSON, Department of Physiology, Queen’s University, Kingston, Ontario, Canada MIRCEA BANCILA, Laboratoire de Neurobiologie de Signaux Intercellulaires, Institut des Neurosciences, Université Pierre et Marie Curie, Paris, France GIORGIO CARMIGNOTO, Department of Experimental Biomedical Sciences, University of Padova, Padova, Italy SOPHIE CHABOT, Department of Oncology and Clinical Neurosciences, University of Calgary, Calgary, Canada VIRGINIA CORNEA-HÉBERT, Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, Canada MARC DEL BIGIO, Department of Pathology, Health Sciences Centre and University of Manitoba, Winnipeg, Canada LAURENT DESCARRIES, Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, Canada STEPHEN DOMBROWSKI, Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland, OH ANDREAS FAISSNER, Laboratoire de Neurobiologie du Developpment et de la Regeneration, Strasbourg, France ALASTAIR V. F ERGUSON, Department of Physiology, Queen's University, Kingston, Ontario, Canada KJELL FUXE, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden JEREMY GARWOOD, Laboratoire de Neurobiologie du Developpment et de la Regeneration, Strasbourg, France ALBERT GJEDDE, The Pathophysiology and Experimental Tomography Center, Aarhus General Hospital, Aarhus C, Denmark NICOLAS HECK, Centre National De la Recherche Scientifique, Strasbourg, France D AMIR JANIGRO, Division of Cerebrovascular Research, Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland, OH ANDERS JANSSON, Department of Neuroscience, Division of Cellular and Molecular Neurochemistry, Karolinska Institute, Stockholm, Sweden ix [...]... is of the same order as the unstressed heart and renal cortex.” These two contrasting views are not necessarily contradictory Whether or not the brain has higher energy requirements than other tissues, the brain is unique, both in its energy-demanding functions and the limitations on the types of fuels it uses and their routes of delivery The above statements are also indicative of the reason brain- energy... developed into a separate specialty, in which the energy supply and demand of the brain are studied as the basis for many brain dysfunctions and disorders The past 15 years witnessed several discoveries and new developments in the field of cerebral energy metabolism, which could explain some of the brain s unique energy requirements, and provide a better understanding of various brain disorders 1.1 Neuronal. .. sacrificed, leaving the composition of extracellular fluids in the brain at the mercy of the brain cells themselves The subsequent necessity to shield the central nervous system from uncontrolled systemic influences, and in order to minimize the extravasation of potentially noxious or osmotically active molecules from the blood, is perhaps the best-understood reason for the creation of the blood brain- barrier... present in the cerebral spinal fluid (26–28) Part of this process is energy-dependent, and directly impacts the ionic homeostasis for potassium ions (see Subheading 3.) Vascular smooth muscle are also indirectly involved in the control of brain homeostasis, since their powerful effect on the control of cerebral perfusion will be the final determinant of the amount of oxygen and glucose delivered to the brain, ... for any other potential energy substrate Clarke and Sokoloff (7) warn their readers about the discrepancies between in vivo and in vitro results concerning brain tissue, and the great hazard of extrapolating from in vitro data to conclusions about in vivo metabolic function In vitro systems bypass functions, such as blood flow, but the uniqueness of the brain in vivo stems from the blood brain barrier... terminals Of the multiple transport processes that take place in the brain, ion transport is believed to demand the most energy (as high as 50–60% of all brain- energy-consuming processes) (1) Of these, the maintenance of sodium ions (Na+) and potassium ions (K+) gradients is the most demanding Unlike other tissues, the central nervous system (CNS) stores only minute amounts of endogenous fuel Brain. .. lactate remains in the brain, and could later be used aerobically for energy metabolism under resting conditions Other recent studies show significant increases in lactate levels in human visual cortex (7,8) and in rat hippocampus and striatum, on physiological stimulation (9) Thus, although the impermeability of the BBB to lactate is irrelevant, since the bulk of brain lactate is produced in the brain itself,... Energy-Demanding Functions, and Energy Substrates 1.1.1 Neuronal Energy Requirements and Energy-Demanding Functions The majority of the energy-demanding reactions in the brain belong to two categories: biosynthesis and transport The biosynthesis of macromolecules, such as proteins, polypeptides, and lipids, occurs mostly in cell bodies; that of smaller molecules, such as neurotransmitters, occurs in nerve... metallothioneins I + II in brainstem of adult rats treated with 6-aminonicotinamide Brain Res 774, 256–259 38 Tsukamoto, H., Hamada, Y., Wu, D., Boado, R J., and Pardridge, W M (1998) GLUT1 glucose transporter: differential gene transcription and mRNA binding to cytosolic and polysome proteins in brain and peripheral tissues Brain Res Mol Brain Res 58, 170–177 39 Lauger, P (1991) Na,K-ATPase, in Electrogenic... of potassium homeostasis performed by astrocytes (24,25) 2.2 Vascular Endothelium and Smooth Muscle In addition to parenchymally located glial cells, at least two additional cell types participate in the process of the control of the composition of the extracellular space in the brain: the cellular elements constituting intraparenchymal vessels, the endothelial cells lining the intraluminal portion . contributing to The Neuronal Environment: Brain Homeostasis in Health and Disease have made an attempt not only to explain the normal functioning of these. Disease examines the function of all the components involved, including their perturbation dur- ing major disease states, and relates them to neuronal demands. The