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The last decade has seen an upsurge of information on the role of immune responses in neurodegenerative disorders. In many of these diseases it is still unclear whether the innate and adaptive responses are pathogenic or play a role in repair, and thus understanding their precise roles is key to controlling these diseases by designing immune-therapeutic approaches.
The connection between many neurological diseases is the realisation that the immune and nervous systems are inextricable linked, and that perturbations in this delicate balance are involved in many disorders. This has opened up new avenues for therapeutic approaches to treatment of CNS inflammatory and neurodegenerative disorders. Neuroinflammation and CNS Disorders brings together the very latest information on the interactions between the immune system and central nervous system. The first section of the book highlights the basic concepts in the field whilst the second section, the main body of the book, covers the role of the immune response in specific disorders of the central nervous system.
Neuroinflammation and CNS Disorders will provide an invaluable guide for both researchers and clinicians working in this complex and dynamic field.
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Veröffentlichungsjahr: 2014
Edited by
Nicola Woodroofe
Sheffield Hallam University
Sandra Amor
VU Amsterdam
This edition first published 2014 © 2014 by John Wiley & Sons, Ltd
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Library of Congress Cataloging-in-Publication Data
Neuroinflammation and CNS disorders / [edited by] Nicola Woodroofe and Sandra Amor. p. ; cm. Includes bibliographical references and index. ISBN 978-1-118-40641-0 (cloth) I. Woodroofe, Nicola, editor of compilation. II. Amor, Sandra, editor of compilation.
[DNLM: 1. Neurodegenerative Diseases–immunology. 2. Autoimmune Diseases– physiopathology. 3. Central Nervous System Diseases–immunology. 4. Central Nervous System Diseases–physiopathology. 5. Inflammation–physiopathology. WL 358.5] RC521 616.8′3–dc23
2013049796
A catalogue record for this book is available from the British Library.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.
Cover image: Courtesy of Steve Gschmeissner www.theworldcloseup.com
List of Contributors
Preface
Introduction: Interactions between the Immune and Central Nervous Systems
Origins
By invitation only
Cross-talk between the immune system and CNS
Of mice and men
Immune responses and neurodegenerative disorders
Acknowledgements
References
About the Companion Website
1
Immune Privilege of the Brain
Introduction
The original experiment
Mechanisms of the brain's immune privilege
Concluding remarks
Acknowledgements
References
2
Innate Immunity in the CNS – A Focus on the Myeloid Cell
Introduction to concepts of innate immunity
Cells of the innate immune system
Innate immune cell receptors
Innate immune responses in the CNS
Summary
Conflict of interests
References
3
Adaptive Immune Responses in the CNS
Introduction to concepts of adaptive immunity
Leukocyte populations in the CNS
T cell populations
T lymphocyte subsets
Mediators of the adaptive immune response
MHC expression on cells of the CNS
Antigen presentation in the CNS
Suppression of immune responses in the CNS
Allografts and cytotoxic T cell responses
Summary
References
4
Ageing and the Immune Response in the CNS
Gene expression in the ageing brain
Inflammation as a hallmark of the ageing brain
Microglia
Microglia in the ageing brain
Microglia in the neurogenic niche
Changes in regulation of microglial activation with ageing
Neural contribution to age-associated brain inflammation
Role of astrocytes in age-associated neuroinflammation
Immune cells in the aged brain
Implications of altered neuroinflammation for the ageing brain
References
5
Brain Repair: The Role of Endogenous and Transplanted Neural Stem Cells
Introduction
The homeostatic regulatory role of endogenous NPCs
NPC transplantation as a therapeutic tool to promote brain repair
The bystander effect of transplanted NPCs
Immunomodulatory effects of transplanted NPCs
Neurotrophic effects of transplanted NPCs
Conclusions and perspectives
Acknowledgements
References
6
Neuroinflammation in Alzheimer's, Parkinson's and Huntington's Diseases
General introduction
Alzheimer's disease
Neuroinflammation in Parkinson's disease
Neuroinflammation in Huntington's disease
Conclusions
References
7
CNS Infections
Introduction
Herpes viruses
Picornaviruses
Retroviruses
JC polyoma virus
Prion diseases
Conclusions
References
8
Neuroimmunology of Amyotrophic Lateral Sclerosis
Overview of amyotrophic lateral sclerosis
Mutant superoxide dismutase animal model of ALS
TDP43 animal model of ALS
Proposed mechanisms of motoneuron injury in ALS
Neuroinflammation and mSOD1 mice
Immunologic aspects of ALS: part 1 – microglia
Immunologic aspects of ALS: part 2 – T cells
Immunologic aspects of ALS: part 3 – B cells
Immunologic aspects of ALS: part 4 – astrocytes
Immunologic aspects of ALS: part 5 – cytokines, chemokines and other markers of inflammation in ALS
Immunologic aspects of ALS: part 6 – dendritic cells
Conclusions
References
9
Demyelinating Disorders of the CNS
Introduction
Specific diseases
Conclusion
Conflict of interest
Acknowledgements
References
10
Other Autoimmune Disorders: Systemic Lupus Erythematosus, Primary Sjögren's Syndrome, Gluten-related Neurological Dysfunction and Paraneoplastic Neurological Syndromes
Systemic lupus erythematosus
Primary Sjögren's syndrome
Gluten-related neurological dysfunction
Paraneoplastic neurological syndromes
References
11
Inflammation in the Pathogenesis of Depression
Introduction
A role for the immune system in depressive illness – what is the evidence?
Evidence for activation of the immune system in depressed patients
Stress as a trigger for activating the immune system in depressed patients
Conclusion
Acknowledgements
References
12
Immune Responses in the CNS in Epilepsy
Introduction
Innate immunity in epilepsy
Adaptive immunity in epilepsy
Conclusions
References
13
Inflammatory Mediators and Dysfunction of the Neurovascular Unit following Ischaemia Reperfusion
Focal ischaemia and early mechanisms of injury
Calcium ion homeostasis
Free radical formation
The ischaemic inflammatory response
The neurovascular unit
Blood–brain barrier permeability
References
14
Spinal Cord Injury
Overview of neuroinflammation and spinal cord injury
Role of the innate immune response: neutrophils
Role of the innate immune response: astrocytes
Role of the innate immune response: macrophages
Role of the adaptive immune response: T and B cells
Current clinical approaches
Conclusion
References
15
Immune Responses to Tumours in the CNS
Tumours of the CNS
The inflammatory infiltrate in CNS tumours
Biology of immune responses to CNS tumours
Immunotherapy of CNS tumours
Conclusions
Acknowledgements
References
Index
End User License Agreement
Introduction
Table I.1
Table I.2
Chapter 2
Table 2.1
Chapter 3
Table 3.1
Table 3.2
Chapter 4
Table 4.1
Table 4.2
Chapter 7
Table 7.1
Chapter 9
Table 9.1
Table 9.2
Table 9.3
Table 9.4
Table 9.5
Chapter 10
Table 10.1
Table 10.2
Chapter 12
Table 12.1
Chapter 13
Table 13.1
Cover
Table of Contents
Preface
Introduction
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Sandra Amor
Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands; and Neuroimmunology Unit, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
Jack P. Antel
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
Stanley H. Appel
Department of Neurology, Houston Methodist Neurological Institute, The Houston Methodist Hospital Research Institute, The Houston Methodist Hospital, Houston, Texas, USA
Marco Bacigaluppi
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
Philip A. Barber
Calgary Stroke Program; and Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Alberta, Canada
Jan Bauer
Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria
Ingo Bechmann
Institute of Anatomy, Universität Leipzig, Leipzig, Germany
David R. Beers
Department of Neurology, Houston Methodist Neurological Institute, The Houston Methodist Hospital Research Institute, The Houston Methodist Hospital, Houston, Texas, USA
Amy Birch
Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Imperial College London, London, UK
Hendrikus W.G.M. Boddeke
Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
Erica Butti
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
S. Louise Cosby
Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Medical Biology Centre, Queen's University Belfast, Belfast, UK
Robert R. Crichton
Université Catholique de Louvain, Louvain-la-Neuve, Belgium
Melania Cusimano
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
Donatella De Feo
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
David T. Dexter
Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Imperial College London, London, UK
Bryce A. Durafourt
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
Bart J.L. Eggen
Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
Sareen Galbraith
Department of Clinical Infection, Microbiology & Immunology, Institute of Infection & Global Health, University of Liverpool, Liverpool, UK
John C. Gensel
Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, Kentucky, USA
Paul Gielen
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences (NCMLS), Radboud University Medical Centre, Nijmegen, the Netherlands
Marios Hadjivassiliou
Academic Department of Neurosciences, Royal Hallamshire Hospital, Sheffield, UK
Andrew Harkin
Neuropsychopharmacology Research Group, School of Pharmacy and Pharmaceutical Sciences & Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland
Derek Healy
Wildlife Zoonoses & Vector-borne Diseases Research Group, Animal Health & Veterinary Laboratories Agency, Weybridge, Surrey, UK
Sarosh R. Irani
Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK
Loukia Katsouri
Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Imperial College London, London, UK
Moniek Kattenbelt
Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands
Bethan Lang
Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK
Cecilia Laterza
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
Lenthe Lodder
Department of Neurology, Flevoziekenhuis, Almere, the Netherlands
David Male
Faculty of Science, The Open University, Milton Keynes, UK
Gianvito Martino
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
Arianna Merlini
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
Craig S. Moore
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
Laura Peferoen
Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands
Luca Peruzzotti
Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
Divya D.A. Raj
Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
Alexander Renziehausen
Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Imperial College London, London, UK
Magdalena Sastre
Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Imperial College London, London, UK
Paul van der Valk
Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands
Johannes M. van Noort
Delta Crystallon BV, Leiden, the Netherlands
Annamaria Vezzani
Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy
Roberta J. Ward
Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Imperial College London, London, UK and Biologie du Comportement, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
Pieter Wesseling
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, and VU University Medical Center, Amsterdam, the Netherlands
Nicola Woodroofe
Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK
Weihua Zhao
Department of Neurology, Houston Methodist Neurological Institute, The Houston Methodist Hospital Research Institute, The Houston Methodist Hospital, Houston, Texas, USA
It is widely assumed that the central nervous system is an immune-privileged site, suggesting that antigens gaining entry to the brain and spinal cord do not invoke an immune response.
While this idea was first discussed over 70 years ago, it is clear that immune privilege is not absolute since immune responses do take place in the central nervous system and are crucial for shaping the brain during development and for controlling infections in the brain. As well as these examples, in the last decade there has been an explosion of information on the role of immune responses in neurodegenerative disorders. In many of these diseases, it is still unclear whether the innate and adaptive responses are pathogenic or play a role in repair, and thus understanding their precise roles is key to controlling these diseases by designing immune-therapeutic approaches.
It is for this reason that we undertook the task of compiling the latest information on the interactions between the immune system and central nervous system.
In the first section of this book, the chapters are dedicated to the communication between the immune system and the central nervous system that is best exemplified by cross-talk between glia and neurons shown to be essential for maintaining homeostasis. This section is specifically designed as an introduction to the topic and forms the basis for the second section devoted to specific neurological diseases.
We are indebted to our many colleagues who have taken time from their busy schedules to help us compile this book. In particular, we would like to especially thank Stan Appel and his team, who underwent the hardship of tragically losing a colleague, Jenny Henkel, during the production of the chapter. Likewise, we also sincerely thank Andrew Harkin, who took over from Tom O'Connor who lost his life during the writing of their chapter. We hope that their memory will live on through their work and help inspire new generations in their fields.
We are not unaware that this will not be the last work on how the immune system interacts with the central nervous system, but we are confident that this book forms the basis of what is to come in the field.
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