The Neuronal Environment Contemporary

The Neuronal Environment: Highly Selective Neurotoxins: Basic and Homeostasis in Health and Disease, Clinical Applications, edited by edited by Wolfgang WaIz, 2002 Richard M. Kostrzewa, 1998 Transporters: Neuroinflammation: Mechanisms and Structure, Function, and Regulation, Management, edited by Paul L. 21e, edited by Maarten E. A. Reith, Wood, 1998 2002 Neuroprotective Signal Transduction, Pathogenesis ofNeurodegenerative edited by Mark P. Mattson, 1998 Disorders, edited by Mark P. Mattson, Clinical Pharmacology of Cerebral 2001 Ischemia, edited by Gert J. Ter Horst Stem Cells and CNS Development, edited and Jakob Korf, 1997 by Mahendra S. Rao, 2001 Molecular Mechanisms of Dementia, Neurobiology of Spinal Cord Injury, edited by Wilma Wasco and edited by Robert G. Kalb and Rudolph E. Tanzi, 1997 Stephen M. Strittmatter, 2000 Neurotransmitter Transporters: Cerebral Signal Transduction: From Structure, Function, and Regulation, First to Fourth Messengers, edited by edited by Maarten E. A. Reith, 1997 Maarten E. A. Reith, 2000 Motor Activity and Movement Disorders: Central Nervous System Diseases: Research Issues and Applications, Innovative Animal Models from Lab to edited by Paul R. Sanberg, Clinic, edited by Dwaine F. Emerich, Klaus-Peter Ossenkopp, and Reginald L. Dean, III, Martin Kavaliers, 1996 and Paul R. Sanberg, 2000 Neurotherapeutics: Emerging Mitochondrial Inhibitors and Strategies, edited by Linda M. Pullan Neurodegenerative Disorders, edited and Jitendra Patel, 1996 by Paul R. Sanberg, Hitoo Nishino, Neuron-Glia Interrelations During and Cesario V. Borlongan, 2000 Phylogeny: II. Plasticity and Cerebral Ischemia: Molecular and Regeneration, edited by Antonia Cellular Pathophysiology, edited by Vernadakis and Betty I. Roots, 1995 Wolfgang Walz, 1999 Neuron-Glia Interrelations During Cell Transplantation for Neurological Phylogeny: I. Phylogeny and Disorders, edited by Ontogeny of Glial Cells, edited by Thomas B. Freeman and Antonia Vernadakis and Hakan Widner, 1998 Betty I. Roots, 1995 Gene Therapy for Neurological The Biology of Neuropeptide Yand Disorders and Brain Tumors, edited Related Pep tides, edited by E. Antonio Chiocca and by William F. Colmers and Xandra O. Breakefield, 1998 Claes Wahlestedt, 1993 The Neuronal Environment

Brain Homeostasis in Health and Disease

Edited by Wolfgang Walz Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Springer Science+Business Media, LLC * © 2002 Springer Science+Business Media New York Originally published by Humana Press Inc. in 2002. Softcover reprint of tbe hardcover 1st edition 2002

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Cover Illustration: Figure 9 from Chapter 4, "Transmitter-Receptar Mismatches in Central Dopamine, Serotonin, and Neuropeptide Systems," Further Evidencejor Va/urne Transmission, by A. Jensson, L. Descarries, V. Cornea-Hebert, M. Riad, D. Verge, M. Bancila, L. F. Agnati, and K. Fluxe.

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Library of Congress Cataloging in Publication Data

The neuronal environment: brain homeostasis in health and diease/ edited by W olfgang Walz p. cm.--(Contemparary neuroscience) Includes bibliographical references and index. ISBN 978-1-61737-235-3 ISBN 978-1-59259-108-4 (eBook) DOI 10.1007/978-1-59259-108-4 1. Neurons--Physiology. 2. Homeostasis. 3. Neuroglia. 4. Brain--Metabolism. 5. Blood-brain barrier. 1. 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 eNS, 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 Vl Preface

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 Contents

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 Sykova 4 Transmitter-Receptor Mismatches in Central Dopamine, Serotonin, and Neuropeptide Systems: Further Evidence for Volume Transmission ...... 83 Anders Jansson, Laurent Descarries, Virginia Cornea-Hebert, Mustapha Riad, Daniel Verge, 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 vii Vlll 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. IMMUNE 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 MrRCEA BANCILA, Laboratoire de Neurobiologie de Signaux Intercellulaires, Institut des , Universite Pierre et Marie Curie, , France GIORGIO CARMIGN01O, Department of Experimental Biomedical Sciences, University of Pad ova, Padova, Italy SOPHIE CHABOT, Department of Oncology and Clinical Neurosciences, University of Calgary, Calgary, Canada VIRGINIA CORNEA-HEBERT, Departement de Pathologie et Biologie Cellulaire, Universite de Montreal, Montreal, Canada MARC DEL BIGIO, Department of Pathology, Health Sciences Centre and University of Manitoba, Winnipeg, Canada LAURENT DESCARRIES, Departement de Pathologie et Biologie Cellula ire, Universite de Montreal, Montreal, Canada . STEPHEN DOMBROWSKI, Department of , Cleveland Clinic Foundation, Cleveland, OH ANDREAS FAISSNER, Laboratoire de Neurobiologie du Developpment et de la Regeneration, Strasbourg, France ALASTAIR V. FERGUSON, 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 DAMIR 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 x Contributors

BERNHARD H.J. JUURLINK, Department of Anatomy and Cell Biology, University Saskatchewan, Saskatoon, Canada HIROYUKI KATO, Department of and Neuroendovascular Therapy, Tohoku University School of Medicine, Sendai, Japan RICHARD F. KEEP, Departments of Surgery and Physiology, , Ann Arbor, MI JEFFERY D. KOCSIS, Neuroscience Research Center, Department of Veterans Affairs Medical Center, Yale University School of Medicine, West Haven, CT IMAD NAJM, Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland,OH TAKANORI OIKAWA, Department of Neurology, Tohoku University School of Medicine, Sendai, Japan MUSTAPHA RrAD, Departement de Pathologie et Biologie Cellulaire, Universite de Montreal, Montreal, Canada FRANCK RrGATO, Centre Natioanl De la Recherche Scientifique, Strasbourg, France AVITAL SCHURR, Department of Anesthesiology, University of Louisville, School of Medicine, Louisville, KY EVA SYKovA, Department of Neuroscience, Institute of Experimental Medicine, Academy of Sciences, Prague, Czech Republic DANIEL VERGE, Laboratoire de Neurobiologie de Signaux Intercellulaires, Institut des Neurosciences, Universite Pierre et Marie Curie, Paris, France WOLFGANG WALZ, Department of Physiology, University of Saskatchewan, Saskatoon, Canada Roy O. WELLER, Department of Microbiology and Pathology, Southhampton General Hospital, Southampton, UK V. WEE YONG, Departments of Oncology and Clinical Neurosciences, University of Calgary, Calgary, Canada MICAELA ZONTA, Department of Experimental Biomedical Sciences, University of Padova, Padova, Italy