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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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Neuroinflammation and CNS Disorders

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

CONTENTS

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

List of Tables

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

Guide

Cover

Table of Contents

Preface

Introduction

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List of Contributors

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

Preface

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.

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!

Lesen Sie weiter in der vollständigen Ausgabe!