Brain and Host Defense (eBook)

Front Cover 1
The Brain and Host Defense 4
Copyright Page 5
Contents 6
Foreword 8
Preface 12
List of Contributors 14
Section I: Introduction 16
Chapter 1 The Hypothalamus is the Central Organ of Immunoregulation 18
1 INTRODUCTION 18
2 SIGNALING THE HYPOTHALAMUS BY THE IMMUNE SYSTEM 18
3 NEUROIMMUNOREGULATION DURING HOMEOSTASIS 20
4 NEUROGENIC INFLAMMATION (NIF) 21
5 THE ACUTE PHASE RESPONSE (APR) 21
6 HEALING 22
7 CONCLUSIONS 22
REFERENCES 23
Section II: Development and Function of the Neuroimmune System 26
Chapter 2 Leech Neuroimmune Signaling 28
1 INTRODUCTION 28
2 NEUROIMMUNE MODULATION BY OPIOIDS 28
3 NEUROIMMUNE MODULATION BY OPIATES 31
4 NEUROIMMUNE MODULATION BY CANNABINOIDS 33
5 BRAIN INNATE IMMUNE RESPONSE 34
6 CONCLUSIONS 35
ACKNOWLEDGEMENTS 35
REFERENCES 35
Chapter 3 Morphogenesis of the Hypothalamus and Hypophysis 40
1 INTRODUCTION 40
2 MORPHOLOGICAL ASPECTS OF PITUITARY DEVELOPMENT 40
3 THE PITUITARY PRIMORDIUM AS A MEMBER OF THE CRANIAL PLACODES 42
4 MOLECULAR ASPECTS OF THE DEVELOPMENT OF ADENOHYPOPHYSEAL PLACODE 44
5 SIGNALING MOLECULES ACTING BEFORE AND AFTER THE FORMATION OF "RATHKE'S POUCH" 44
6 TRANSCRIPTION FACTORS WORKING IN DEVELOPING PITUITARY CELLS 45
7 ADENOHYPOPHYSIS AND ITS HOMOLOGS IN AGNATHAN VERTEBRATES AND PROTOCHORDATES 47
REFERENCES 48
Chapter 4 A Novel Genus of Specialized Anti-Inflammatory and Pro-Resolution Lipid Mediators 52
1 INFLAMMATION 52
2 RESOLUTION OF SELF-LIMITED ACUTE INFLAMMATION 53
3 ANTI-INFLAMMATORY AND PRO-RESOLUTION LIPID MEDIATORS 54
4 RESOLVINS 58
5 PROTECTINS AND D-SERIES RESOLVINS 58
6 MARESINS 63
7 CONCLUSIONS 65
8 SUMMARY 65
ACKNOWLEDGEMENTS 65
REFERENCES 65
Chapter 5 Neural and Non-Neural Stem Cells as Novel Therapeutic Modalities for Brain Injury 74
1 INTRODUCTION 74
2 NEURAL STEM CELLS 74
3 NON-NEURONAL (ADULT) STEM CELLS IN THE CNS 77
REFERENCES 78
Chapter 6 The Role of the Toll-Like Receptors in Neuropathology 82
1 INTRODUCTION 82
2 IMMUNE-LINKED RECEPTORS IN THE BRAIN 82
3 STRUCTURE OF TLRS 82
4 TLR ADAPTOR PROTEINS 83
5 STROKE/ISCHEMIC BRAIN DAMAGE 85
6 INVADING PATHOGENS 85
7 CANCER 86
8 SPINAL CORD INJURY 86
9 ALZHEIMER'S DISEASE 87
10 MULTIPLE SCLEROSIS 88
11 NEUROPATHIC PAIN 88
12 CONCLUSIONS 89
REFERENCES 90
FURTHER READING 92
Chapter 7 Cytokines and the Immune–Neuroendocrine Network 94
1 INTRODUCTION 94
N.....i.................................................. 97
3 Th1 CYTOKINES IN THE NEUROIMMUNE NETWORK 99
4 REGULATORY CYTOKINES IN THE NEUROIMMUNE NETWORK 99
5 CYTOKINES AND MAJOR DEPRESSION 100
6 CONCLUDING REMARKS 100
ACKNOWLEDGEMENTS 101
REFERENCES 101
Chapter 8 Orexin-Containing Neurons and the Immune System 106
1 INTRODUCTION 106
2 OREXIN AND OREXINERGIC NEURONS 106
3 OREXINERGIC NEURON PROJECTIONS 107
4 OREXIN RECEPTORS 108
5 HYPOTHALAMIC OREXIN-CONTAINING NEURONS AND CYCLOPHOSPHAMIDE ADMINISTRATION 110
6 OREXIN-CONTAINING NEURONS RESPOND TO ANTIGENIC CHALLENGES 110
CONCLUSION 112
REFERENCES 112
Chapter 9 Central Pathways of Immunoregulation 116
1 CENTRAL PATHWAYS OF IMMUNOREGULATION 116
E.................u...C..............r................... 116
E.................u...C..............r................... 116
E.................u...C..............r................... 118
5 DESCENDING NEURAL PATHWAYS FROM THE PVN TO IMMUNE END ORGANS 119
6 RECRUITMENT OF PRE-SYMPATHETIC NUCLEI 119
7 DESCENDING CONNECTIONS FROM PRE-SYMPATHETIC TO PREGANGLIONIC CELLS 121
8 INNERVATION OF IMMUNE ORGANS BY SYMPATHETIC PROJECTIONS 121
9 CONCLUSIONS 121
REFERENCES 122
Chapter 10 Brain Responses to Antigenic Challenges 128
1 INTRODUCTION 128
2 NEUROPHYSIOLOGICAL PROCESSES IN HYPOTHALAMIC STRUCTURES DURING IMMUNE RESPONSE DEVELOPMENT 128
3 THE C-FOS GENE AS A MARKER OF ACTIVATION OF NEURONAL CELLS 129
4 C-FOS GENE EXPRESSION IN THE CNS AFTER ANTIGENIC CHALLENGES 130
5 CONCLUSIONS 134
ACKNOWLEDGEMENT 134
REFERENCES 134
Section III: Immunoregulation by the Nervous System 138
Chapter 11 Role of the Endocrine System 140
1 INTRODUCTION 140
2 HPA AXIS AND THE IMMUNE RESPONSE 140
3 OTHER NEUROENDOCRINE AXES AND THE IMMUNE RESPONSE 143
4 CONCLUSIONS 144
REFERENCES 144
Chapter 12 Conditioning of Immune Reactions 146
INTRODUCTION 146
1 EVIDENCE FOR CNS AND IMMUNE SYSTEM INTERACTIONS 146
2 CONDITIONING OF IMMUNITY IN ANIMAL MODEL SYSTEMS 148
3 POSSIBLE MECHANISMS FOR MEDIATING CLASSICAL CONDITIONING OF IMMUNE RESPONSES 151
4 SUMMARY AND DISCUSSION 155
ACKNOWLEDGEMENT 156
REFERENCES 156
Chapter 13 Gender Issues in Host Defense 160
1 INTRODUCTION 160
2 HOST DEFENSE 160
3 GENDER ISSUES IN HOST DEFENSE MECHANISMS 161
4 IMMUNE-DEPRESSIVE EFFECTS OF MALE SEX STEROIDS 165
5 POTENTIAL IMMUNE-MODULATORY MECHANISMS OF SEX STEROIDS 167
6 THERAPEUTIC OPTIONS 168
7 CONCLUSIONS 169
REFERENCES 170
Section IV: How the Brain Defends Itself 174
Chapter 14 Glial Cells in Brain Defense Mechanisms 176
1 INTRODUCTION: GLIAL CELLS IN THE BRAIN 176
2 MICROGLIA 176
3 CANDIDATE NEURON–MICROGLIA SIGNALING FACTORS 178
4 CONCLUSIONS 180
REFERENCES 180
Chapter 15 Immunologic Privilege and the Brain 184
1 INTRODUCTION 184
2 DEFINING THE BRAIN AS AN IMMUNOLOGICALLY PRIVILEGED SITE: HISTORICAL ROOTS 185
3 COMPONENTS OF IMMUNOLOGIC PRIVILEGE 186
4 LYMPHOCYTE TRAFFICKING 189
5 DOWNREGULATION OF INTRA-CNS IMMUNE RESPONSES 192
6 CONCLUSION 192
REFERENCES 193
Chapter 16 Immune Aspects of the Blood–Brain Barrier 198
1 INTRODUCTION TO THE BLOOD–BRAIN BARRIER 198
2 ENDOTHELIAL CELL ACTIVATION 200
3 PERICYTES: THE SECOND LINE OF DEFENSE 203
4 ASTROCYTE–BARRIER INDUCTIVE EFFECTS 205
5 CONCLUSION 206
REFERENCES 207
Chapter 17 Neuroprotective Activities of CD4[sup(+)]CD25[sup(+)] Regulatory T Cells 212
1 INTRODUCTION 212
2 HISTORICAL PERSPECTIVE 213
3 DEVELOPMENT OF TREGS 213
4 MECHANISMS OF REGULATION 213
5 INTERPLAY BETWEEN TH1, TH2, TH17 AND TREG CELLS 215
6 ADAPTIVE IMMUNITY AND NEUROPROTECTION 216
7 TREGS ARE PROTECTIVE IN MODELS OF NEURODEGENERATION 216
8 TREGS AND MONONUCLEAR PHAGOCYTE ACTIVATION 217
9 TREGS REGULATE PROTECTIVE IMMUNITY 217
10 INDUCTION OF TREGS WITH ADJUNCTIVE THERAPY 219
11 CONCLUSION 219
REFERENCES 220
Section V: The Role of the Brain in Host Defense in Disease States 226
Chapter 18 Fever as a Host Defense Mechanism 228
1 INTRODUCTION 228
2 DEFINITION OF FEVER 228
3 FEVER: AN OLD WEAPON OF MASS PROTECTION 228
4 THE COURSE AND CHARACTER OF FEVER 229
5 THERMOEFFECTOR MECHANISMS OF FEBRIGENESIS AND FEBRILYSIS 230
6 THE PYROGENIC STIMULUS 231
7 THE NEURAL SUBSTRATE OF FEVER PRODUCTION AND LYSIS 233
8 PUTATIVE MEDIATORS OF FEVER 234
9 IMMUNONEUROMODULATION OF FEVER: UPDATED CONCEPT 236
10 CONCLUSIONS 243
ACKNOWLEDGEMENTS 244
REFERENCES 244
Chapter 19 Leukocytes as Mediators of Pain and Analgesia 252
1 INTRODUCTION 252
2 PROALGESIC MECHANISMS 252
3 ANALGESIC MECHANISMS 256
REFERENCES 262
Chapter 20 Tumor Necrosis Factor as a Neuroinflammatory Mediator in Alzheimer's Disease and Stroke: Molecular Mechanisms and Neuroinflammatory Imaging 266
1 INTRODUCTION 266
2 SOME BASIC ASPECTS OF CEREBRAL INFLAMMATION 267
3 COMMON INFLAMMATORY FEATURES IN NORMAL BRAIN 268
4 INFLAMMATORY SIGNALS IN NEURODEGENERATIVE DISORDERS AND STROKE: MARKERS FOR DAMAGE OR PROTECTION? 268
5 NEUROINFLAMMATORY IMAGING 269
6 INFLAMMATORY MOLECULES AS POSSIBLE DRUG TARGETS FOR NOVEL THERAPEUTIC STRATEGIES 272
7 NEUROINFLAMMATION, MICROGLIAL ACTIVATION AND NEURODEGENERATION: ADDITIONAL PATHWAYS 276
8 NEUROINFLAMMATION: CAN INFLAMMATION LEAD TO IMPROVEMENTS IN DIAGNOSIS AND TREATMENT OF NEURODEGENERATIVE DISEASES? 277
REFERENCES 278
Chapter 21 Multiple Sclerosis and Depression: A Neuroimmunological Perspective 284
1 INTRODUCTION 284
2 FREQUENCY OF DEPRESSION IN MS 284
3 DEPRESSION PRIOR TO ONSET OF MS 285
4 FAMILY HISTORY OF DEPRESSION IN MS 285
5 DEPRESSION AT ONSET OF MS 286
6 DEPRESSION IN ELDERLY MS PATIENTS 286
7 CLINICAL FEATURES OF DEPRESSION IN MS 287
8 SYMPTOMS SHARED BETWEEN DEPRESSION AND MS 287
9 CLINICAL CORRELATIONS 288
10 SUICIDE IN MS 288
11 MIGRAINE AND MS 289
12 BRAIN METABOLISM IN DEPRESSION 289
13 BRAIN METABOLISM IN MS 290
14 MRI, DEPRESSION AND MS 291
15 THE HYPOTHALAMIC–PITUITARY–ADRENAL (HPA) AXIS IN DEPRESSION 291
16 THE HPA AXIS IN MS 295
17 BIPOLAR DISEASE 297
18 THE IMMUNOLOGY OF MULTIPLE SCLEROSIS 298
19 CYTOKINES IN DEPRESSION AND THE EFFECT OF ANTIDEPRESSANTS ON CYTOKINES 300
20 BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) IN DEPRESSION AND IN MS 304
21 CORTICOTROPHIN-RELEASING HORMONE (CRH) IN PERIPHERAL TISSUES 305
22 DOES DEPRESSION COMPLICATE TREATMENT OF MS WITH IMMUNOMODULATORY DRUGS? 306
23 MANAGEMENT OF DEPRESSION IN PEOPLE WITH MS 308
ACKNOWLEDGEMENTS 309
REFERENCES 309
Chapter 22 Infection and Sepsis 324
1 HOST IMMUNE RESPONSES DURING INFECTION AND SEPSIS 324
2 BRAIN-TO-IMMUNE PATHWAYS THAT REGULATE HOST RESPONSES DURING INFECTION 326
3 SUMMARY AND CONCLUSION 331
ACKNOWLEDGEMENTS 332
REFERENCES 332
Chapter 23 Restoration of Neuroimmune Disturbances in Rats by Extra-High-Frequency Electromagnetic Irradiation of the Skin 336
1 INTRODUCTION 336
2 NK CELL ACTIVITY AND EXPRESSION OF THE C-FOS GENE IN HYPOTHALAMIC STRUCTURES OF RATS AFTER PAINFUL ELECTRIC STIMULATION OF THE LIMBS: THE EFFECT OF EHF SKIN IRRADIATION 337
3 C-FOS GENE EXPRESSION, MORPHOFUNCTIONAL CHANGES IN OREXIN-CONTAINING NEURONS IN HYPOTHALAMIC STRUCTURES AND NK CELL ACTIVITY IN… 339
4 LIPOPOLYSACCHARIDE-INDUCED ACTIVATION OF HYPOTHALAMIC OREXIN-CONTAINING NEURONS IN RATS, NATURAL KILER CELL CYTOTOXICITY AND THE… 342
5 CONCLUSIONS 343
ACKNOWLEDGEMENTS 344
REFERENCES 344
Subject Index 348
A 348
B 349
C 349
D 350
E 350
F 351
G 351
H 351
I 352
J 353
K 353
L 353
M 354
N 355
O 355
P 355
Q 356
R 356
S 356
T 357
U 358
V 358
W 358
Z 358
Color Plates 360