Neuroinflammation has long been studied for its connection to the development and progression of Multiple Sclerosis. In recent years, the field has expanded to look at the role of inflammatory processes in a wide range of neurological conditions and cognitive disorders including stroke, amyotrophic lateral sclerosis, and autism. Researchers have also started to note the beneficial impacts of neuroinflammation in certain diseases.

Neuroinflammation: New Insights into Beneficial and Detrimental Functions provides a comprehensive view of both the detriments and benefits of neuroinflammation in human health.

Neuroinflammation: New Insights into Beneficial and Detrimental Functions opens with two chapters that look at some fundamental aspects of neuroinflammation in humans and rodents. The remainder of the book is divided into two sections which examine both the detrimental and beneficial aspects of inflammation on the brain, spinal cord and peripheral nerves, on various disease states, and in normal aging. These sections provide a broad picture of the role neuroinflammation plays in the physiology and pathology of various neurological disorders.

Providing cross-disciplinary coverage, Neuroinflammation: New Insights into Beneficial and Detrimental Functions will be an essential volume for neuroimmunologists, neurobiologists, neurologists, and others interested in the field.

Samuel David is a Professor at the Centre for Research in Neuroscience at The Research Institute of the McGill University Health Centre in Montreal, Quebec, Canada.

List of Contributors xi

Preface xvii

PART I Introduction 1

1 Immune Response in the Human Central Nervous System in Multiple Sclerosis and Stroke 3
Hans Lassmann

Introduction 3

The Concept of Neuroinflammation 3

Basic Principles of Immune Surveillance and Inflammation by Adaptive Immune Responses 4

Inflammation in the Central Nervous System of Patients with Multiple Sclerosis 7

Inflammation in Stroke Lesions 11

Microglia Activation and Macrophage Response 12

Granulocyte Infiltration 12

Conclusions 15

References 15

2 In Vivo Imaging of Glial and Immune Cell Responses in Central Nervous System Injury and Disease 21
Alexandre Paré and Steve Lacroix

Introduction 21

Intravital Microscopy in the CNS and Its Challenges 22

In Vivo Imaging of the CNS Following Sterile Injury 24

In Vivo Imaging of the CNS in Disorders with an Inflammatory Component 27

Conclusion 32

Acknowledgments 33

References 33

PART II Detrimental Aspects of Inflammation 39

3 Roles of CD4 and CD8 T Lymphocytes in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis 41
Nathalie Arbour and Alexandre Prat

Introduction 41

T Lymphocytes: Central Immune Cells 42

Autoreactive T Lymphocytes 42

From Peripheral Activation to CNS Extravasation 45

Role of CD4 T Lymphocytes in MS and EAE: Th1 versus Th17 46

Role of CD8 T Lymphocytes in MS and EAE 47

Regulatory T Lymphocytes in MS and EAE 48

Conclusions 49

Acknowledgements 49

References 49

4 Microglia and Macrophage Responses and Their Role after Spinal Cord Injury 53
Antje Kroner, Andrew D. Greenhalgh, and Samuel David

Introduction 53

Microglial Responses to Injury 54

Interactions between Microglia and Other Cell Types in Signaling Responses to Injury 57

Entry of Peripheral Macrophages and Differences with Microglia 59

Diverse Roles of Macrophages/Microglia in CNS Injury and Disease 60

Macrophage Polarization in SCI 61

Concluding Remarks 66

Acknowledgements 66

References 66

5 The Complexity of the Innate Immune System Activation in Stroke Pathogenesis 71
María Isabel Cuartero, Ignacio Lizasoain, María Ángeles Moro, and Ivan Ballesteros

Activation of the Brain Innate Immunity After Stroke 71

Myeloid Heterogeneity in Brain Ischemia 76

Concluding Remarks 81

References 81

6 Neuroinflammation in Aging 87
Ashley M. Fenn, Diana M. Norden, and Jonathan P. Godbout Increased CNS Inflammation in Response to Immune Challenge is Adaptive and Beneficial 87

The CNS Microenvironment Shifts to a Proinflammatory State with Aging 88

Microglial Priming 88

Microglial Regulation 90

Immune Reactivity of Glia Contributes to Cognitive and Behavioral Deficits 97

Conclusions 100

References 100

7 Peripheral and Central Immune Mechanisms in Neuropathic Pain 107
Ji Zhang

Introduction 107

Inflammation in Neuropathic Pain 108

Contribution of Peripheral Immune Cells to the Pathogenesis of Neuropathic Pain 109

Critical Roles of Spinal Glial Activation in Neuropathic Pain 111

Significance of Neural Barriers in Inflammatory Response along Pain Transmission Pathway 114

Imbalance of Pro- and Anti-inflammatory Responses in Neuropathic Pain 115

Challenges in Translating Anti-inflammatory Therapeutic Strategies for the Relief of Neuropathic Pain 115

Acknowledgement 117

References 117

8 Inflammation in the Pathogenesis of Inherited Peripheral Neuropathies 123
Janos Groh, Dennis Klein, Antje Kroner, and Rudolf Martini

Inherited Peripheral Neuropathies 123

Subtype-Specific Molecular Patterns of CMT1 124

Molecular Commonalities of CMT1 Subtypes-a Link to Inflammation 125

The Impact of Innate Immune Reactions in Mouse Models of CMT1 126

The Impact of Adaptive Immune Reactions in Mouse Models of CMT1 129

Implications for Putative Therapeutic Approaches 130

Synopsis 132

Acknowledgements 132

References 133

9 Obesity- and Neuroinflammation-Associated Mood and Cognitive Disorders 139
Nathalie Castanon, Giamal Luheshi, and Sophie Layé

Introduction 139

Neuropsychiatric Comorbidity in Obesity 140

Animal Models of Obesity and MetS 140

Mechanisms Underlying the Association between Obesity/MetS and Neuropsychiatric Symptoms 142

Neuroinflammation, Sickness Behavior, and Neuropsychiatric Symptoms 143

Role of Neuroinflammation in Neuropsychiatric Symptoms Associated with Obesity and MetS 146

Conclusions 148

References 149

10 Viral Infections of the Central Nervous System: Pathogenic and Protective Effects of Neuroinflammation 155
John G. Walsh and Christopher Power

Introduction 155

Nervous System Infection and Inflammation 157

HIV-1 Infection: Neurological and Neuropathological Features 158

WNV Infection and Neuropathology 162

Future Perspectives 166

References 167

PART III Beneficial Aspects of Inflammation 173

11 The Interplay between the Peripheral and Local Immune Response in Recovery from Acute Central Nervous System Injuries 175
Catarina Raposo and Michal Schwartz

Paradigm of Protective Autoimmunity 175

Dichotomy between Microglia and Infiltrating Monocyte-Derived Macrophages 176

Infiltrating Macrophages Promote Inflammation Resolution and Axonal Regeneration 177

The Two Faces of Tregs in CNS Repair 178

Protective Autoimmunity Works at the Specialized Choroid Plexus Gate 179

Inflammation, the Old Villain in Spinal Cord Repair 181

Comprehensive View of the Protective Autoimmune Network: the Link between Autoimmune T Cells and Inflammation-Resolving Cells 181

Acknowledgments 183

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