NEUROINFLAMMATION Mechanisms and Management S ECOND E DITION Edited by P AUL L. W OOD HUMANA PRESS N EUROINFLAMMATION Contemporary Neuroscience Neuroinflammation: Mechanisms and Man- agement, Second Edition, edited by Paul L. Wood, 2003 Neurobiology of Aggression: Understanding and Preventing Violence, edited by Mark P. Mattson, 2003 Neural Stem Cells for Brain and Spinal Cord Repair, edited by Tanja Zigova, Evan Y. Snyder, and Paul R. Sanberg, 2003 Neurotransmitter Transporters: Structure, Function, and Regulation, Second Edition, edited by Maarten E. A. Reith, 2002 The Neuronal Environment: Brain Homeostasis in Health and Disease, edited by Wolfgang Walz, 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 Neurodegenera- tive Disorders, edited by Paul R. Sanberg, Hitoo Nishino, and Cesario V. Borlongan, 2000 Cerebral Ischemia: Molecular and Cellular Patho- physiology, edited by Wolfgang Walz, 1999 Cell Transplantation for Neurological Disor- ders, edited by Thomas B. Freeman and Håkan Widner, 1998 Gene Therapy for Neurological Disorders and Brain Tumors, edited by E. Antonio Chiocca and Xandra O. Breakefield, 1998 Highly Selective Neurotoxins: Basic and Clini- cal Applications, edited by Richard M. Kostrzewa, 1998 Neuroinflammation: Mechanisms and Man- agement, edited by Paul L. Wood, 1998 Neuroprotective Signal Transduction, edited by Mark P. Mattson, 1998 Clinical Pharmacology of Cerebral Ischemia, edited by Gert J. Ter Horst and Jakob Korf, 1997 Molecular Mechanisms of Dementia, edited by Wilma Wasco and Rudolph E. Tanzi, 1997 Neurotransmitter Transporters: Structure, Func- tion, and Regulation, edited by Maarten E. A. Reith, 1997 Motor Activity and Movement Disorders: Research Issues and Applications, edited by Paul R. Sanberg, Klaus-Peter Ossenkopp, and Martin Kavaliers, 1996 Neurotherapeutics: Emerging Strategies, edited by Linda M. Pullan and Jitendra Patel, 1996 Neuron–Glia Interrelations During Phylog- eny: II. Plasticity and Regeneration, edited by Antonia Vernadakis and Betty I. Roots, 1995 The Biology of Neuropeptide Y and Related Peptides, edited by William F. Colmers and Claes Wahlestedt, 1993 NEUROINFLAMMATION Mechanisms and Management S ECOND E DITION HUMANA PRESS TOTOWA, NEW JERSEY Edited by PAUL L. WOOD Oxon Medica South San Francisco, CA © 2003 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 www.humanapress.com All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. The content and opinions expressed in this book are the sole work of the authors and editors, who have warranted due diligence in the creation and issuance of their work. The publisher, editors, and authors are not responsible for errors or omissions or for any consequences arising from the information or opinions presented in this book and make no warranty, express or implied, with respect to its contents. Cover Illustration: Figure 4 from Chapter 16, “The Neuroinflammatory Components of the Trimethyltin (TMT) Model of Hippocampal Neurodegeneration,” by G. Jean Harry and Christian Lefebvre d’Hellencourt. Production Editor: Jessica Jannicelli. Cover design by Patricia F. Cleary. 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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 $20.00 per copy 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 Reporting Service is: [1-58829-002-6/03 $20.00]. Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 Library of Congress Cataloging-in-Publication Data Neuroinflammation : mechanisms and management / edited by Paul L. Wood 2nd ed. p. ; cm. (Contemporary neuroscience) Includes bibliographical references and index. ISBN 1-58829-002-6 (alk. paper) 1-59259-297-X (e-book) 1. Nervous system Degeneration Immunological aspects. 2. Inflammation. 3. Neuritis. 4. Inflammation Mediators. 5. Nervous system Pathophysiology. I. Wood, Paul L. II. Series. [DNLM: 1. Neurodegenerative Diseases immunology. 2. Anti-Inflammatory Agents pharmacology. 3. Inflammation immunology. 4. Nerve Degeneration immunology. 5. Neurodegenerative Diseases drug therapy. WL 359 N49483 2003] RC363 .N48 2003 616.8’0479 dc21 2002038760 PREFACE v The first edition of Neuroinflammation: Mechanisms and Management was the first book to organize the early concepts of neuroinflammatory mechanisms and the role of these processes in complex neurodegenerative diseases. The field is unique in the neu- roscience area in that it has required the skills and experimental analyses of an extremely diverse array of scientific and clinical research groups. This field includes publications from neurologists, psychiatrists, pathologists, clinical imaging groups, neurophysiolo- gists, neurochemists, immunologists, molecular biologists, anatomists, biochemists, and pharmacologists. This field has also generated excitement in both academic and pharma- ceutical research arenas, and since the last edition of this book, has resulted in the intro- duction of two novel inhibitors of neuroinflammation into clinical trials. These include CEP-1347 for Parkinson’s disease and CPI-1189 for Alzheimer’s disease. Both com- pounds are currently in Phase II clinical trials, and pivotal efficacy data should be avail- able within the next 3 years. In the second edition, we have included extensive updates of new knowledge of the mediators produced by activated microglia and their role in neuroinflammatory-induced neuronal lysis. In addition, we have increased the coverage of animal models used in the study of neuroinflammatory mechanisms and in the new imaging methods that allow the noninvasive evaluation of microglial activation in human neurodegenerative disorders. These imaging techniques have demonstrated that microglial activation and the associated neuroinflammation precedes neuronal degeneration in a number of clinical conditions. Another important aspect of neuroinflammation that has evolved since the first edition of this book is the role of neuroinflammation in amyloid-dependent neuronal lysis. Both in vitro and in vivo data indicate that amyloid is unlikely to be directly neurotoxic, but that amyloid deposition activates neuroinflammatory processes that lead to neuronal degeneration. In summary, the field of neuroinflammation is evolving rapidly and advancing new potential therapeutics into clinical trials. When scientific concepts result in drugs with clinical utility, a research field has achieved significant maturity and productivity. I hope that this maturity, and its benefit to the treatment of devastating neurological disorders, is solidly in place for the next edition of Neuroinflammation: Mechanisms and Management. Paul L. Wood Preface v Contributors ix I. NEUROINFLAMMATORY MECHANISMS 1 Microglia: Roles of Microglia in Chronic Neurodegenerative Diseases 3 Paul L. Wood 2 Apoptosis vs Nonapoptotic Mechanisms in Neurodegeneration 29 Kurt A. Jellinger 3 Role(s) of Mitogen and Stress-Activated Kinases in Neurodegeneration 89 Christopher C. J. Miller, Steven Ackerley, Janet Brownlees, Andrew J. Grierson, and Paul Thornhill 4 Roles of Chemokines and Their Receptors in Neuroinflammation 99 Andrzej R. Glabinski and Richard M. Ransohoff 5 Neurotoxic Mechanisms of Nitric Oxide 117 Kathleen M. K. Boje 6 Chronic Intracerebral LPS as a Model of Neuroinflammation 137 Gary L. Wenk and Beatrice Hauss-Wegrzyniak 7 Peroxisome Proliferator-Activated Receptor Gamma Agonists: Potential Therapeutic Agents for Neuroinflammation 151 Gary E. Landreth, Sophia Sundararajan, and Michael T. Heneka 8 Neuroinflammation-Mediated Neurotoxin Production in Neurodegenerative Diseases: Potential of Nitrones as Therapeutics 171 Robert A. Floyd and Kenneth Hensley II. STROKE AND TBI 9 Inflammation and Potential Anti-Inflammatory Approaches in Stroke 189 Jari Koistinaho and Juha Yrjänheikki 10 Neuroinflammation as an Important Pathogenic Mechanism in Spinal Cord Injury 215 Yuji Taoka and Kenji Okajima 11 Type IV Collagenases and Blood-Brain Barrier Breakdown in Brain Ischemia 237 Yvan Gasche, Jean-Christophe Copin, and Pak H. Chan CONTENTS vii III. ALZHEIMER’S DISEASE 12 Neuroinflammatory Environments Promote Amyloid-β Deposition and Posttranslational Modification 249 Craig S. Atwood, Mark A. Smith, Ralph N. Martins, Rudolph E. Tanzi, Alex E. Roher, Ashley I. Bush, and George Perry 13 Microglial Responses in Alzheimer’s Disease: Recent Studies in Transgenic Mice and Alzheimer’s Disease Brains 267 Douglas G. Walker and Lih-Fen Lue 14 The Amyloid Hypothesis of Cognitive Dysfunction 283 Dave Morgan and Marcia N. Gordon 15 The Cerebellum in AD: A Case for Arrested Neuroinflammation? 295 Paul L. Wood 16 The Neuroinflammatory Components of the Trimethyltin (TMT) Model of Hippocampal Neurodegeneration 301 G. Jean Harry and Christian Lefebvre d’Hellencourt 17 Inflammation and Cyclo-Oxygenase in Alzheimer’s Disease: Experimental Approaches and Therapeutic Implications 331 Patrick Pompl, Tara Brennan, Lap Ho, and Giulio Maria Pasinetti IV. MULTIPLE SCLEROSIS 18 Experimental Autoimmune Encephalomyelitis 345 Hans-Peter Hartung and Bernd C. Kieseier 19 Neuroimmunologic Mechanisms in the Etiology of Multiple Sclerosis 359 Claudia F. Lucchinetti, W. Brück, and Hans Lassmann 20 In Vivo Imaging of Neuroinflammation in Neurodegenerative Diseases 379 Annachiara Cagnin, Alexander Gerhard, and Richard B. Banati V. PARKINSON’S AND HUNTINGTON’S DISEASES 21 Inflammatory Mechanisms in Parkinson’s Disease 391 Joseph Rogers and Carl J. Kovelowski 22 Neuroinflammatory Components of the 3-Nitropropionic Acid Model of Striatal Neurodegeneration 405 Hideki Hida, Hiroko Baba, and Hitoo Nishino Index 417 viii Contents STEVEN ACKERLEY • Departments of Neuroscience and Neurology, Institute of Psychiatry, Kings College London, Denmark Hill, London, UK C RAIG S. ATWOOD • Institute of Pathology, Case Western Reserve University, Cleveland, OH H IROKO BABA • Department of Physiology, Nagoya City University School of Medicine, Nagoya, Japan R ICHARD B. BANATI • Clinical Sciences Centre, PET-Neurology, Hammersmith Hospital; and Division of Neuroscience and Psychological Medicine, Department of Neuropathology (Molecular Neuropsychiatry), Faculty of Medicine, Imperial College, London, UK K ATHLEEN M. K. BOJE • Department of Pharmaceutical Sciences, SUNY Buffalo School of Pharmacy, Buffalo, NY T ARA BRENNAN • Neuroinflammation Research Laboratories, Department of Psychiatry, Mount Sinai School of Medicine, New York, NY J ANET BROWNLEES • Departments of Neuroscience and Neurology, Institute of Psychiatry, Kings College London, Denmark Hill, London, UK W. B RÜCK • Department of Neuropathology, Charité, Humboldt University, Berlin, Germany A SHLEY I. BUSH • Laboratory for Oxidation Biology, Genetics and Aging Unit, Department of Psychiatry, Harvard Medical School, Boston, MA A NNACHIARA CAGNIN • Clinical Sciences Centre, PET-Neurology, Hammersmith Hospital, London, UK; and Department of Neurological Sciences, Padua University, Padua, Italy P AK H. CHAN • Neurological Laboratories, Stanford University, Stanford, CA J EAN-CHRISTOPHE COPIN • Neurological Laboratories, Stanford University, Stanford, CA; and Divisions of Surgical and Medical Critical Care, Geneva University Hospital, Geneva, Switzerland C HRISTIAN LEFEBVRE D’HELLENCOURT • Neurotoxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC R OBERT A. FLOYD • Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation; and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK Y VAN GASCHE • Neurological Laboratories, Stanford University, Stanford, CA; and Divisions of Surgical and Medical Critical Care, Geneva University Hospital, Geneva, Switzerland A LEXANDER GERHARD • Clinical Sciences Centre, PET-Neurology, Hammersmith Hospital, London, UK A NDRZEJ R. GLABINSKI • Department of Neurology, Medical University of Lodz, Lodz, Poland M ARCIA N. GORDON • Department of Pharmacology, Alzheimer’s Research Laboratory, University of South Florida, Tampa, FL A NDREW J. GRIERSON • Academic Neurology Unit, The Medical School, University of Sheffield, Sheffield, UK CONTRIBUTORS ix [...]... act to elicit microglial activation are numerous and are related to the normal “housekeeping” functions of microglia As immunocompetent cells, a number of chemotactic factors are potential modulators of microglial migration and activation Receptors on microglia have been demonstrated for a number From: Neuroinflammation, 2nd Edition: Mechanisms and Management Edited by: P L Wood © Humana Press Inc.,... Arends, Y M., Duyckaerts, C., Rozemuller, J M., Eikelenboom, P., and Hauw, J J (2000) Microglia, amyloid and dementia in Alzheimer disease—a correlative study Neurobiol Aging 21, 39–47 28 McGeer, P L., McGeer, E G., and Yasojima, K (2000) Alzheimer disease and neuroinflammation J Neural Transm 59, 53–57 29 Sheffield, L G., Marquis, J G., and Berman, N J (2000) Regional distribution of cortical microglia... 95–102 64 Li, H., Newcombe, J., Groome, P., and Cuzner, M L (1993) Characterization and distribution of phagocytic macrophages in multiple sclerosis plaques Neuropathol Appl Neurobiol 19, 214–223 65 Bö, L., Mork, S., Kong, P A., Nyland, H., Pardo, C A., and Trapp, B D (1994) Detection of MHC class II-antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis... with neuronal and neuritic beta-amyloid precursor protein expression Neurosci Lett 176, 133–136 20 Wood 104 Takeuchi, A., Miyaishi, O., Kiuchi, K., and Isobe, K (2001) Macrophage colony-stimulating factor is expressed in neuron and microglia after focal brain injury J Neurosci Res 65, 38–44 105 Mautes, A E M and Noble, L J (2000) Co-induction of HSP70 and heme oxygenase-1 in macrophages and glia after... 129 Sebire, G., Hery, C., Peudenier, S., and Tardieu, M (1993) Adhesion proteins on human microglial cells and modulation of their expression by IL1-alpha and TNF-alpha Res Virol 144, 47–52 130 Cannella, B and Raine, C S (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions Ann Neurol 37, 424–435 131 Ryan, R., Sloane, B F., Sameni, M., and Wood, P L (1995) Microglial cathepsin... Immunocompetent astrocytes and microglia display major differences in the processing of the invariant chain and in the expression of active cathepsin L and cathepsin S Eur J Immunol 31, 1813–1824 135 Yoshiyama, Y., Arai, K., Oki, T., and Hattori, T (2000) Expression of invariant chain and pro-cathepsin L in Alzheimer’s brain Neurosci Lett 290, 125–128 136 Liuzzo, J P., Petanceska, S S., and Devi, L A (1999)... Q., Banos, M A., Herregodts, P., Hooghe, R., and Hooghe-Peters, E L (1992) Expression of interleukin (IL)-1β, IL-6 and their respective receptors in the normal rat brain and after injury Eur J Immunol 22, 2963–2971 162 Castrell, J V., Andus, T., Kunz, D., and Heinrich, P C (1989) Interleukin-6: the major regulator of acute-phase protein synthesis in man and rat Ann NY Acad Sci 557, 87–101 163 Wood,... T., Kondo, H., Ikeda, K., Hayashi, Y., and McGeer, P L (1994) Expression of the receptor for macrophage colony stimulating factor by brain microglia and its upregulation in brains with Alzheimer’s disease and amyotrophic lateral sclerosis Brain Res 639, 171–174 22 Mrak, R E., Sheng, J G., and Griffin, W S T (1995) Glial cytokines in Alzheimer’s disease: review and pathogenic implications Hum Pathol... cell population within the entire neuroaxis and represent the primary immunocompetent cells to deal with invasions by infectious agents and tumors and to remove cellular debris These cells are present in large numbers representing 10–20% of the glial cell population in the brain and, in the case of perivascular microglia, may play a role in antigen recognition and processing at the level of the bloodbrain... expressed in viable astrocytes and mircoglia but in degenerating pyramidal neurons in the kainate-lesioned rat hippocampus Exp Brain Res 137, 424–431 42 Finsen, B R., Jorgensen, M B., Diemer, N H., and Zimmer, J (1993) Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus Glia 7, 41–49 43 Andersson, P.-B., Perry, V H., and Gordon, S (1991) The CNS acute . NEUROINFLAMMATION Mechanisms and Management S ECOND E DITION Edited by P AUL L. W OOD HUMANA PRESS N EUROINFLAMMATION Contemporary Neuroscience Neuroinflammation: Mechanisms and Man- agement,. 2002038760 PREFACE v The first edition of Neuroinflammation: Mechanisms and Management was the first book to organize the early concepts of neuroinflammatory mechanisms and the role of these processes. Brownlees, Andrew J. Grierson, and Paul Thornhill 4 Roles of Chemokines and Their Receptors in Neuroinflammation 99 Andrzej R. Glabinski and Richard M. Ransohoff 5 Neurotoxic Mechanisms of Nitric Oxide