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 xiPreface xviiPART I Introduction 11 Immune Response in the Human Central Nervous System in Multiple Sclerosis and Stroke 3Hans LassmannIntroduction 3The Concept of Neuroinflammation 3Basic Principles of Immune Surveillance and Inflammation by Adaptive Immune Responses 4Inflammation in the Central Nervous System of Patients with Multiple Sclerosis 7Inflammation in Stroke Lesions 11Microglia Activation and Macrophage Response 12Granulocyte Infiltration 12Conclusions 15References 152 In Vivo Imaging of Glial and Immune Cell Responses in Central Nervous System Injury and Disease 21Alexandre Paré and Steve LacroixIntroduction 21Intravital Microscopy in the CNS and Its Challenges 22In Vivo Imaging of the CNS Following Sterile Injury 24In Vivo Imaging of the CNS in Disorders with an Inflammatory Component 27Conclusion 32Acknowledgments 33References 33PART II Detrimental Aspects of Inflammation 393 Roles of CD4 and CD8 T Lymphocytes in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis 41Nathalie Arbour and Alexandre PratIntroduction 41T Lymphocytes: Central Immune Cells 42Autoreactive T Lymphocytes 42From Peripheral Activation to CNS Extravasation 45Role of CD4 T Lymphocytes in MS and EAE: Th1 versus Th17 46Role of CD8 T Lymphocytes in MS and EAE 47Regulatory T Lymphocytes in MS and EAE 48Conclusions 49Acknowledgements 49References 494 Microglia and Macrophage Responses and Their Role after Spinal Cord Injury 53Antje Kroner, Andrew D. Greenhalgh, and Samuel DavidIntroduction 53Microglial Responses to Injury 54Interactions between Microglia and Other Cell Types in Signaling Responses to Injury 57Entry of Peripheral Macrophages and Differences with Microglia 59Diverse Roles of Macrophages/Microglia in CNS Injury and Disease 60Macrophage Polarization in SCI 61Concluding Remarks 66Acknowledgements 66References 665 The Complexity of the Innate Immune System Activation in Stroke Pathogenesis 71María Isabel Cuartero, Ignacio Lizasoain, María Ángeles Moro, and Ivan BallesterosActivation of the Brain Innate Immunity After Stroke 71Myeloid Heterogeneity in Brain Ischemia 76Concluding Remarks 81References 816 Neuroinflammation in Aging 87Ashley M. Fenn, Diana M. Norden, and Jonathan P. Godbout Increased CNS Inflammation in Response to Immune Challenge is Adaptive and Beneficial 87The CNS Microenvironment Shifts to a Proinflammatory State with Aging 88Microglial Priming 88Microglial Regulation 90Immune Reactivity of Glia Contributes to Cognitive and Behavioral Deficits 97Conclusions 100References 1007 Peripheral and Central Immune Mechanisms in Neuropathic Pain 107Ji ZhangIntroduction 107Inflammation in Neuropathic Pain 108Contribution of Peripheral Immune Cells to the Pathogenesis of Neuropathic Pain 109Critical Roles of Spinal Glial Activation in Neuropathic Pain 111Significance of Neural Barriers in Inflammatory Response along Pain Transmission Pathway 114Imbalance of Pro- and Anti-inflammatory Responses in Neuropathic Pain 115Challenges in Translating Anti-inflammatory Therapeutic Strategies for the Relief of Neuropathic Pain 115Acknowledgement 117References 1178 Inflammation in the Pathogenesis of Inherited Peripheral Neuropathies 123Janos Groh, Dennis Klein, Antje Kroner, and Rudolf MartiniInherited Peripheral Neuropathies 123Subtype-Specific Molecular Patterns of CMT1 124Molecular Commonalities of CMT1 Subtypes–a Link to Inflammation 125The Impact of Innate Immune Reactions in Mouse Models of CMT1 126The Impact of Adaptive Immune Reactions in Mouse Models of CMT1 129Implications for Putative Therapeutic Approaches 130Synopsis 132Acknowledgements 132References 1339 Obesity- and Neuroinflammation-Associated Mood and Cognitive Disorders 139Nathalie Castanon, Giamal Luheshi, and Sophie LayéIntroduction 139Neuropsychiatric Comorbidity in Obesity 140Animal Models of Obesity and MetS 140Mechanisms Underlying the Association between Obesity/MetS and Neuropsychiatric Symptoms 142Neuroinflammation, Sickness Behavior, and Neuropsychiatric Symptoms 143Role of Neuroinflammation in Neuropsychiatric Symptoms Associated with Obesity and MetS 146Conclusions 148References 14910 Viral Infections of the Central Nervous System: Pathogenic and Protective Effects of Neuroinflammation 155John G. Walsh and Christopher PowerIntroduction 155Nervous System Infection and Inflammation 157HIV-1 Infection: Neurological and Neuropathological Features 158WNV Infection and Neuropathology 162Future Perspectives 166References 167PART III Beneficial Aspects of Inflammation 17311 The Interplay between the Peripheral and Local Immune Response in Recovery from Acute Central Nervous System Injuries 175Catarina Raposo and Michal SchwartzParadigm of Protective Autoimmunity 175Dichotomy between Microglia and Infiltrating Monocyte-Derived Macrophages 176Infiltrating Macrophages Promote Inflammation Resolution and Axonal Regeneration 177The Two Faces of Tregs in CNS Repair 178Protective Autoimmunity Works at the Specialized Choroid Plexus Gate 179Inflammation, the Old Villain in Spinal Cord Repair 181Comprehensive View of the Protective Autoimmune Network: the Link between Autoimmune T Cells and Inflammation-Resolving Cells 181Acknowledgments 183References 18312 Inflammation and Optic Nerve Regeneration 189Lukas Andereggen, Ephraim F. Trakhtenberg, Yin Yuqin, and Larry I. BenowitzIntroduction 189Background 190Effects of inflammation on RGC survival and Optic Nerve Regeneration 192Oncomodulin as a Key Mediator of Inflammation-Induced Regeneration 193Synergistic Effects of Combinatorial Treatments 198Conclusions 200Acknowledgments 200References 20013 Effects of Macrophages and Monocytes in Remyelination of the CNS 205Muktha Natrajan, Bibiana Bielekova, and Robin J.M. FranklinIntroduction 205Myelin Debris Inhibits OPC Differentiation and Remyelination 207Monocyte-Derived Macrophages are the Main Actors in Myelin Debris Phagocytosis 209Switching from M1 to M2 Macrophages Promotes CNS Remyelination 211Ageing Impairs Macrophage Function, Myelin Debris Clearance, and Remyelination 212Macrophages Release Growth and Neurotrophic Factors that Promote Remyelination 213Concluding Remarks 215References 21514 Microglia Involvement in Rett Syndrome 221Noël C. Derecki, James C. Cronk, and Jonathan KipnisIntroduction to Rett Syndrome and MeCP2 221Experimental Mouse Models Used in the Study of Rett Syndrome 222The Cellular Players in Central Nervous System Pathology of Rett Syndrome 223Microglia: From Footnote to First-Line 224Microglia: the Tissue-Resident Macrophages of the Brain 225Replacement/Augmentation of MICROGLIA as A potential therapy in Rett Syndrome 228Gene Therapy 229Conclusions 230References 23015 The Role of Regulatory T Cells and Microglia in Amyotrophic Lateral Sclerosis 235David R. Beers, Weihua Zhao, Kristopher G. Hooten, and Stanley H. AppelOverview of Amyotrophic Lateral Sclerosis 235Overview of ALS Animal Models 237Overview of Regulatory T Cells 238Immunologic Aspects of Microglia and Tregs in ALS 240T Cells and ALS 242Tregs and ALS 243Cytokines and ALS 244Conclusions 245References 24716 An Adaptive Role for TNFin Synaptic Plasticity and Neuronal Function 251Renu Heir and David StellwagenIntroduction 251Developmental Roles of TNFα 252TNFα in Presynaptic Function 252TNFα effects on postsynaptic receptor trafficking 252TNFα and Synaptic Plasticity 255Glial Release of TNFα During Plasticity 256TNFα-mediated homeostatic plasticity in vivo 258TNFα-Mediated Plasticity in the Striatum 258Implications of TNFα-Mediated Synaptic Regulation 259References 26017 Resolution of Inflammation in the Lesioned Central Nervous System 265Jan M. Schwab, Harald Prüss, and Charles N SerhanIntroduction 265Mechanisms of Resolution 267Resolution Deficit Following CNS Lesions 268Immunobiology of Resolution in CNS Lesions–Impaired Resolution Contributes to Neuropathology 269Late Degeneration/“Tertiary” Injury and Autoimmunity as a Consequence of Failed Resolution of Inflammation in CNS Lesions? 271Evidence for the Effectiveness of Pro-resolution Mediators in CNS Lesions 273Conclusion 274Acknowledgement 275References 275Index 281