CNS Injuries: Cellular Responses and Pharmacological Strategies

CNS Injuries: Cellular Responses and Pharmacological Strategies......Page 1
Preface......Page 3
Editors......Page 5
Contributors......Page 6
Table of Contents......Page 8
1.1 Introduction......Page 10
Table of Contents......Page 0
1.2.1 Acute Haemorrhagic Phase– 0 to 3Days Postinjury (Figure 1.1)......Page 11
1.2.2 Subacute Phase– 3 to 8Days Postinjury (Figure 1.1)......Page 13
1.2.2.1 Reaction of Astrocytes to Injury......Page 14
1.2.2.3 Reaction of Microglia to Injury......Page 16
1.3 Inflammation/Scarring Responses to Injury in the Foetal/Neonatal CNS......Page 17
1.4 Responses of Neurons to Injury......Page 18
References......Page 20
2.1 Introduction......Page 28
2.2.1 Early Responses......Page 29
2.2.2 Differential Astrocyte Responses......Page 30
2.3.1 Breakdown of the Blood-Brain Barrier......Page 31
2.3.2 Smooth Muscle and the Tunica Media......Page 32
2.3.3 Endothelial Responses......Page 33
2.3.5 Long-Term Changes......Page 35
2.4.1 Time Course......Page 36
2.5.1 Neuronal Susceptibility......Page 37
2.5.2 Two Types of Neuronal Response......Page 38
2.5.3.2 Cytoskeletal Proteolysis......Page 40
2.5.3.4 Excitotoxicity......Page 41
2.7 Concluding Remarks......Page 43
References......Page 45
3.1 Introduction......Page 51
3.2 Primary Immune Response to Antigens in the CNS......Page 54
3.2.1 Responses to Soluble Antigens......Page 55
3.2.2 Responses to Insoluble Antigens......Page 56
3.2.3 Antigen Presentation to the Immune System......Page 57
3.2.4 Injury and Autoimmunity......Page 58
3.3 Injury and the Accessibility of the Brain to the Immune System......Page 60
3.4 Summary and Concluding Remarks......Page 62
References......Page 63
4.1 Introduction......Page 70
4.2.2 Cytokines and Chemokines......Page 71
4.2.3 Neutrophils and Tissue Damage......Page 72
4.3 Macrophages and Tissue Injury in the CNS......Page 73
4.3.1 Contribution of Microglia......Page 74
4.3.3 Cytotoxic Activity of Microglia......Page 75
4.4.1 Pathological Features of MS Lesions......Page 76
4.4.3 T Lymphocytes and Recognition of CNS Autoantigens......Page 77
4.4.4 T Lymphocytes, Cytokines, and Macrophages......Page 78
References......Page 79
5.1 Introduction......Page 88
5.2 Relationship Between Microglia and Brain Macrophages......Page 89
5.2.1.1 The Normal Developing Brain......Page 90
5.2.1.2 The Pathological Developing Brain......Page 94
5.2.2.1 The Normal Adult Brain......Page 95
5.2.2.2 The Pathological Adult Brain......Page 98
5.4 Can Microglia and Macrophages Promote CNS Regeneration?......Page 100
References......Page 101
6.1 Introduction......Page 105
6.2 Molecular Basis of Leucocyte- endothelial Interactions......Page 107
6.2.2.1 Intercellular Adhesion Molecules1 and -2......Page 108
6.2.3.2 PSelectin and ESelectin......Page 109
6.2.4 Lymphocyte Migration Across Blood Vessel Walls at Inflammatory Lesions......Page 110
6.3 Vascular Adhesion Molecules in the CNS......Page 111
6.4 Characterisation of Lymphocytes that Migrate Across the Blood–Brain Barrier......Page 112
6.5 Antibody Blocking Studies......Page 114
6.6 Future Strategies......Page 115
References......Page 117
7.1 History, Origin, and Distribution of Microglia in the Normal Retina......Page 126
7.2 Methodological Assessment of Microglia......Page 128
7.2.5 Phagocytosis-Dependent Labelling......Page 129
7.2.6 In Vitro Studies......Page 130
7.3 Function During Development and Natural Apoptosis......Page 132
7.4 Retinal Diseases Associated with Microglia......Page 134
7.5 Heterogeneity of Microglial Activation......Page 136
7.6.1 Antimetabolites and Protease Inhibitors......Page 138
7.6.2 Antibodies to Microglial Antigens and Cell Inhibitors......Page 143
7.7.1 Neurotrophins......Page 144
7.7.2 Immunosuppressing Drugs......Page 145
7.7.3 Hormone-Derived Microglial Inhibitors......Page 146
Glossary of Abbreviations......Page 147
References......Page 148
8.1 Glial Scar Formation in the CNS......Page 156
8.2.1 Molecular Structure of TGF-bs......Page 159
8.2.2 TGF-b Receptors......Page 162
8.2.3.2 Formation of Extracellular Matrix......Page 163
8.2.3.5 Angiogenesis......Page 164
8.4 TGF-b Expression in CNS Wounds......Page 165
8.5 Experimental Modulation of TGF-b Activity in CNS Wounds......Page 167
8.6 Conclusions......Page 169
References......Page 170
9.1 Introduction......Page 174
9.2.1 General Aspects of Neurotrophic Factors......Page 175
9.2.2 Neurotrophins......Page 177
9.2.4 Glial Cell Line-Derived Neurotrophic Factor......Page 178
9.3.1.1 Neurotrophins......Page 179
9.3.1.2 CNTF and GDNF......Page 182
9.3.2.1 Neurotrophins......Page 184
9.3.2.2 CNTF and GDNF......Page 185
9.3.3 RETINAL GANGLION CELLS......Page 186
9.4.1.1 Sprouting and Neurotropism......Page 187
9.4.1.3 CNS Terrain and Reinnervation......Page 188
9.4.2.1 Central Sensory Axons......Page 189
9.4.2.2 Corticospinal Motor Axons......Page 191
9.5 STRATEGIES FOR NEUROTROPHIC FACTOR DELIVERY......Page 192
REFERENCES......Page 193
10.1 The Fibroblast Growth Factor (FGF) Family......Page 206
10.2 Distribution of FGFs in the Intact CNS......Page 207
10.3 Expression of FGFs in the Injured and Diseased CNS......Page 209
10.4 Effects of FGFs In Vivo And In Vitro......Page 210
10.5 FGFs and the Treatment of CNS Injuries......Page 212
References......Page 213