Lavi / Constantinescu Experimental Models of Multiple Sclerosis

1. Auflage 2008
ISBN: 978-0-387-25518-7
Verlag: Springer-Verlag
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 902 Seiten

Multiple Sclerosis (MS) is an enigmatic immune mediated disease of the central nervous system that affects about 350,000 individuals in the US, and many more around the world. The mechanism of this disease is largely unknown and there is no cure for it. However, there are several well-characterized experimental animal models that help us understand and speculate about potential mechanisms of pathology in this disease. Many of the experimental therapies designed for this disease rely on testing the drugs in animal models before using it in clinical trials. This book combines for the first time the different experimental models for MS (including immune-mediated and viral) under one roof, and highlights aspects that are different or shared among these experimental models. It's aim is to improve our understanding of this devastating disease and help us think about potential additional therapies for it.

Autoren/Hrsg.

Lavi, Ehud

Constantinescu, Cris

Inhaltsverzeichnis

1;Contents;5
2;Dedication;9
3;Preface Experimental Models of Multiple Sclerosis;10
4;Part A EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS (EAE) (AUTOIMMUNE);12
4.1;Chapter A1 EAE: HISTORY, CLINICAL SIGNS, AND DISEASE COURSE;13
4.1.1;1. INTRODUCTION;13
4.1.2;2. HISTORY;14
4.1.2.1;2.1 Early Studies;14
4.1.2.2;2.2 Identification of encephalitogens;15
4.1.2.3;2.3 Adoptive or passive EAE;16
4.1.2.4;2.4 Relapsing EAE;16
4.1.2.5;2.5 Transgenic models of EAE;17
4.1.3;3. CLINICAL SIGNS AND DISEASE COURSE;18
4.1.4;ACKNOWLEDGEMENTS;19
4.1.5;REFERENCES;19
4.2;Chapter A2 INDUCTION OF EAE;22
4.2.1;1. INTRODUCTION;22
4.2.2;2. EAE INDUCED BY IMMUNIZATION (ACTIVE EAE) OR BY ADOPTIVE T CELL TRANSFER (PASSIVE EAE, AT-EAE);24
4.2.2.1;2.1 Overview;24
4.2.2.2;2.2 Antigenic preparations;25
4.2.2.3;2.3 Active EAE;26
4.2.2.4;2.4 Generation of PLP- or MBP-specific LNCs;27
4.2.2.5;2.6 EAE induced by adoptive T cell transfer (passive EAE, AT-EAE);29
4.2.3;3. CLINICAL MANIFESTATION AND EVALUATION OF DISEASE;30
4.2.4;3. DISCUSSION;31
4.2.5;ACKNOWLEDGMENTS;32
4.2.6;References;32
4.3;Chapter A3 HISTOPATHOLOGY OF EAE;36
4.3.1;1. BASIC MICROANATOMY OF THE CENTRAL NERVOUS SYSTEM;36
4.3.2;2. BASIC CNS HISTOPATHOLOGY;38
4.3.2.1;2.1 Inflammation;38
4.3.2.2;2.2 Demyelination;38
4.3.3;3. EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;39
4.3.3.1;3.1 EAE as a model of MS;40
4.3.4;4. HISTOPATHOLOGY OF EAE;42
4.3.4.1;4.1 EAE in SJL/J mice;44
4.3.4.2;4.2 EAE in C57B1/6 mice;45
4.3.4.3;4.3 EAE in the NOD mouse;47
4.3.4.4;4.4 EAE in the Lewis rat;48
4.3.4.5;4.4 EAE in rhesus monkeys and marmosets;50
4.3.4.6;ACKNOWLEDGEMENTS;51
4.3.4.7;REFERENCES;51
4.4;Chapter A4 NEUROANTIGENS IN EAE;55
4.4.1;1. INTRODUCTION;55
4.4.2;2. THE CELL BIOLOGY OF MYELIN;56
4.4.3;3. THE BIOCHEMISTRY OF MYELIN;57
4.4.3.1;3.1 Myelin lipids and their synthetic enzymes;57
4.4.3.2;3.2 Myelin proteins;60
4.4.3.3;3.3 Myelin associated glycoprotein (MAG);68
4.4.3.4;3.4 Oligodendrocyte specific protein (OSP; aka Claudin- 11);70
4.4.3.5;3.5 Myelin oligodendrocyte protein (MOG);70
4.4.3.6;3.6 Connexin 32 (Cx32; Gap junction [~ 1);70
4.4.3.7;3.7 The paranodal junction proteins (septate-like junctions);71
4.4.3.8;3.8 Other proteins;71
4.4.4;4. CONCLUSIONS;72
4.4.4.1;ACKNOWLEGDMENT;72
4.5;Chapter A5 ADJUVANTS IN EAE;83
4.5.1;ACKNOWLEDGEMENTS;89
4.5.2;REFERENCES;89
4.6;Chapter A6 THE ROLE OF ASTROCYTES IN AUTOIMMUNE DISEASE OF THE CENTRAL NERVOUS SYSTEM;95
4.6.1;ACKNOWLEDGEMENTS;106
4.6.2;REFERENCES;106
4.7;Chapter A7 ROLE OF MICROGLIA AND MACROPHAGES IN EAE;119
4.7.1;1. MICROGLIA AND MACROPHAGES IN THE NORMAL BRAIN;120
4.7.2;2. CELLULAR AND MOLECULAR RESPONSE IN EAE AND MS;122
4.7.3;REFERENCES;132
4.8;Chapter A8 THE NEURON AND AXON IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;142
4.8.1;1.1 History o f axonal loss;142
4.8.2;2. AXONAL LOSS IN MS;143
4.8.3;3. AXONAL LOSS IN EAE;148
4.8.4;REFERENCES;154
4.9;Chapter A9 ENDOTHELIAL CELLS AND ADHESION MOLECULES IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;159
4.9.1;1. INTRODUCTION;159
4.9.2;2. INFLAMMATORY CELL MIGRATION IN EAE;160
4.9.3;3. ROLE OF CNS ENDOTHELIAL CELLS IN EAE;162
4.9.4;4. ROLE OF ADHESION MOLECULES IN EAE;166
4.9.5;5. CONCLUSION;179
4.9.6;ACKNOWLEDGMENTS;179
4.9.7;REFERENCES:;179
4.10;Chapter A10 GENETICS OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS;188
4.10.1;1.1 Myelin and the Major Histocompatibility complex in susceptibility to CNS autoimmunity;190
4.10.2;1.2 Non-MHC autosomai susceptibility loci;193
4.10.3;ACKNOWLEDGEMENTS;198
4.10.4;REFERENCES;198
4.11;Chapter A11 T LYMPHOCYTES IN EAE;209
4.11.1;1 EAE AS A T CELL-MEDIATED DISEASE;209
4.11.2;2. CYTOKINES IN EAE;214
4.11.3;3. NON-CD4+ T CELLS IN EAE;217
4.11.4;4. REGULATORY CELLS IN EAE;219
4.11.5;5. STUDIES ON AUTOREACTIVE T CELL DEVELOPMENT AND ACTIVATION;224
4.11.6;6. T CELL-DIRECTED PEPTIDE THERAPY OF EAE;230
4.11.7;7. CONCLUDING REMARKS;234
4.11.8;REFERENCES;234
4.12;Chapter A12 THE ROLE OF COMPLEMENT IN EAE;252
4.12.1;1. THE COMPLEMENT SYSTEM;253
4.12.2;2. COMPLEMENT AND BRAIN INFLAMMATION;257
4.12.3;3. COMPLEMENT IN EAE;258
4.12.4;4. THERAPEUTIC IMPLICATIONS OF COMPLEMENT INVOLVEMENT IN DEMYELINATION;267
4.12.5;REFERENCES;268
4.13;Chapter A13 B CELLS AND ANTIBODIES IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;275
4.13.1;ACKNOWLEDGEMENTS;281
4.13.2;REFERENCES;281
4.14;Chapter A14 CYTOKINES IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;288
4.14.1;ACKNOWLEDGEMENTS;304
4.14.2;REFERENCES;304
4.15;Chapter A15 THE ROLE OF INTERFERONS IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;317
4.15.1;1. INTRODUCTION;318
4.15.2;2. IFN- 7 IN EAE;319
4.15.3;3. INTERFERON- L AND -13 IN EAE;328
4.15.4;4. IFN-TAU IN EAE;332
4.15.5;ACKNOWLEDGMENTS;334
4.15.6;REFERENCE LIST;334
4.16;Chapter A16 THE ROLE OF GROWTH FACTORS IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;347
4.16.1;1. INTRODUCTION;347
4.16.2;2. NEUROTROPHINS;348
4.16.3;3. CILIARY NEUROTROPHIC FACTOR;350
4.16.4;4. GLIAL GROWTH FACTOR;351
4.16.5;5. INSULIN-LIKE GROWTH FACTOR-1;351
4.16.6;6. FIBROBLAST GROWTH FACTOR;354
4.16.7;7. NEUROPROTECTION BY ENCEPHALITOGENIC T CELLS;354
4.16.8;8. CONCLUSION;356
4.16.9;ACKNOWLEDGMENTS;356
4.16.10;9. REFERENCE LIST;356
4.17;Chapter A17 THE CHEMOKINE SYSTEM IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;366
4.17.1;CHEMOKINES AND THEIR RECEPTORS;367
4.17.2;CHEMOKINES IN EAE;369
4.17.3;CHEMOKINE RECEPTORS IN EAE;370
4.17.4;CHEMOKINES IN GENETICALLY MODIFIED ANIMALS WITH EAE;371
4.17.5;EAE IN ANIMALS WITH GENETICALLY MODIFIED CHEMOKINE SYSTEM;372
4.17.6;TREATMENT OF EAE STRATEGY WITH ANTICHEMOKINE;373
4.17.7;CHEMOKINES AND CHEMOKINE RECEPTORS IN MULTIPLE SCLEROSIS;375
4.17.8;CONCLUSIONS;376
4.17.9;REFERENCES;376
4.18;Chapter A18 FREE RADICALS AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;381
4.18.1;ONOO- vs. NO in EAE;386
4.18.2;ACKNOWLEDGEMENTS;390
4.18.3;REFERENCES;390
4.19;Chapter A19 PROTEASES AND PEPTIDASES IN EAE;393
4.19.1;1. INTRODUCTION;393
4.19.2;SUMMARY;410
4.19.3;REFERENCE LIST:;410
4.20;Chapter A20 THE BLOOD-BRAIN BARRIER IN EAE;416
4.20.1;1. INTRODUCTION;416
4.20.2;2. THE PHYSIOLOGICAL BLOOD-BRAIN BARRIER;417
4.20.3;3. THE BLOOD-BRAIN BARRIER DURING EAE;427
4.20.4;4. RECRUITMENT OF ENCEPHALITOGENIC T CELLS ACROSS THE BBB;432
4.20.5;5. THE BLOOD-CEREBROSPINAL FLUID BARRIER IN EAE;439
4.20.6;6. OUTLOOK;439
4.20.7;7. ACKNOWLEDGEMENTS;440
4.20.8;8. REFERENCES;440
4.21;Chapter A21 IMMUNOMODULATION OF EAE: ALTERED PEPTIDE LIGANDS, TOLERANCE, AND TH1/TH2;451
4.21.1;Introduction;451
4.21.2;1. Non-specific strategies;453
4.21.3;2. Antigen-specific strategies;455
4.21.4;Acknowledgments;462
4.21.5;References;463
4.22;Chapter A22 THE ROLE OF COSTIMULATION IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;471
4.22.1;ACKNOWLEDGMENTS;483
4.22.2;REFERENCES;483
4.23;Chapter A23 EPITOPE SPREADING IN EAE;491
4.23.1;Introduction;491
4.23.2;EAE Disease Induction in Studying Epitope Spreading;492
4.23.3;Mouse Models for Examining Epitope Spreading;492
4.23.4;ACKNOWLEDGMENTS;501
4.23.5;REFERENCES;501
4.24;Chapter A24 APOPTOTIC CELL DEATH IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;506
4.24.1;1. INTRODUCTION;506
4.24.2;Acknowledgements;516
4.25;Chapter A25 ENVIRONMENTAL INFLUENCES IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;521
4.25.1;Introduction;521
4.25.2;Trauma;528
4.25.3;Solar radiation;528
4.25.4;Stress;532
4.25.5;Diet;533
4.25.6;Toxins;534
4.25.7;Effects of temperature;535
4.25.8;Hyperbaric oxygen;536
4.25.9;ACKNOWLEDGMENTS;537
4.26;Chapter A26 HORMONAL AND GENDER INFLUENCES ON EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;545
4.26.1;1. Glucocorticoids;546
4.26.2;2. Gender influences on EAE;549
4.26.3;3. Pregnancy;553
4.26.4;4. Other hormones in EAE;554
4.26.5;5. Conclusion;555
4.26.6;ACKNOWLEDGMENTS;555
4.26.7;REFERENCES;555
4.27;Chapter A27 EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN PRIMATES;559
4.27.1;Introduction;559
4.27.2;1. EAE IN THE COMMON MARMOSET;560
4.27.2.1;1.1 The common marmoset;560
4.27.2.2;1.2 Myelin-induced EAE;561
4.27.2.3;1.3 MOG-induced EAE;564
4.27.3;2 MAGNETIC RESONANCE IMAGING;566
4.27.4;3. PATHOLOGY;567
4.27.5;4. CONCLUDING REMARKS;569
4.27.6;ACKNOWLEDGMENTS;569
4.27.7;REFERENCE LIST;570
5;Part B THEILER' S MURINE ENCEPHALOMYELITIS VIRUS (TMEV) - INDUCED DEMYELINATION;575
5.1;Chapter B 1 HISTOPATHOLOGY IN THE THEILER'S VIRUS MODEL OF DEMYELINATION;576
5.1.1;REFERENCES;585
5.2;Chapter B2 TMEV AND NEUROANTIGENS: MYELIN GENES AND PROTEINS, MOLECULAR MIMICRY, EPITOPE SPREADING, AND AUTOANTIBODY-MEDIATED REMYELINATION;589
5.2.1;1. INTRODUCTION;590
5.2.2;2. MYELIN GENES, VIRUS ENTRY, AND VIRUS PERSISTENCE;591
5.2.3;3. HUMORAL AUTOIMMUNE RESPONSES TO MYELIN;594
5.2.4;4. CELLULAR AUTOIMMUNE RESPONSES TO MYELIN;597
5.2.5;5. TMEV INFECTION AS MODELS TO STUDY MOLECULAR MIMICRY AND REMYELINATION;600
5.2.6;6. CONCLUSION;605
5.2.7;ACKNOWLEDGEMENTS;606
5.2.8;REFERENCES;606
5.3;Chapter B 3 THE ROLE OF ASTROCYTES, OLIGODENDROCYTES, MICROGLIA AND ENDOTHELIAL CELLS IN TMEV INFECTION;613
5.3.1;1. INTRODUCTION;613
5.3.2;2. THE ROLE OF CNS GLIA IN TMEV-IDD;614
5.4;Chapter B4 IMMUNOGENETICS, RESISTANCE, AND SUSCEPTIBILITY TO THEILER'S VIRUS INFECTION;625
5.4.1;References;634
5.5;Chapter B5 THE ROLE OF T CELLS AND THE INNATE IMMUNE SYSTEM IN THE PATHOGENESIS OF THEILER'S VIRUS DEMYELIATING DISEASE;641
5.5.1;1. Introduction;642
5.5.2;2. Role of virus-specific T cell responses in disease resistance/ susceptibility;642
5.5.3;3. Role of myelin-specific T cell responses in TMEV-IDD;645
5.5.4;4. TMEV-IDD Model of Molecular Mimicry;646
5.5.5;5. Innate Immune Response Induced by TMEV Infection;648
5.5.6;6. Conclusions;649
5.5.7;7. References;649
5.6;Chapter B6 CYTOKINES, CHEMOKINES AND ADHESION MOLECULES IN TMEV-IDD;654
5.6.1;1. CYTOKINES;655
5.6.2;2. CHEMOKINES;659
5.6.3;3. ADHESION MOLECULES;660
5.6.4;4. ROLE IN PATHOGENESIS OF DISEASE;661
5.7;Chapter B7 MOLECULAR DETERMINANTS OF TMEV PATHOGENESIS;667
5.7.1;INTRODUCTION;667
5.7.2;RECOMBINANT AND MUTANT VIRUS STUDIES;669
5.7.3;THE ROLE OF L* IN TO SUBGROUP STRAIN DISEASE;672
5.7.4;Cell-Type Specific Regulation of L* Synthesis;675
5.7.5;CONCLUSION;675
5.7.6;ACKNOWLEDGMENTS;676
5.7.7;REFERENCES;676
5.8;Chapter B8 NITRIC OXIDE IN TMEV;678
5.8.1;1. INTRODUCTION;679
5.8.2;ACKNOWLEDGEMENTS;686
5.8.3;REFERENCES;686
5.9;Chapter B9 THEILER'S MURINE ENCEPHALOMYELITIS VIRUS (TMEV)-INDUCED DEMYELINATION;690
5.9.1;DEFINITION OF APOPTOSIS;690
5.9.2;Pathways to Cell Death;691
5.9.3;Intrinsic Pathway;692
5.9.4;Extrinsic Pathway;692
5.9.5;TMEV-INDUCED APOPTOSIS;693
5.9.6;PICORNAVIRUS ANTI-APOPTOTIC MECHANISMS;696
5.9.7;ROLE OF APOPTOSIS IN TMEV-INDUCED DEMYELINATING DISEASE;697
6;Part C CORONA VIRUS-INDUCED DEMYELINATION;702
6.1;Chapter C1 HISTOPATHOLOGY IN CORONAVIRUS- INDUCED DEMYELINATION;703
6.1.1;INTRODUCTION;703
6.1.2;MHV INDUCD ACUTE ENCEPHALITIS;704
6.1.3;ACKNOLEDGEMENTS;706
6.1.4;REFERENCES;706
6.2;Chapter C2 THE ROLE OF ASTROCYTES, MICROGLIA, AND ENDOTHELIAL CELLS IN CORONAVIRUS- INDUCED DEMYELINATION;709
6.2.1;1. INTRODUCTION;709
6.2.2;2. Animal models of coronavirus induced demyelination;713
6.2.3;3. The role of astrocytes, microglia, and endothelial cells in MHV-induced CNS demyelination;713
6.2.4;4. CONCLUSIONS;721
6.2.5;References;721
6.3;Chapter C3 AXONS AND NEURONS IN CORONAVIRUS- INDUCED DEMYELINATION;728
6.3.1;1. INTRODUCTION;728
6.3.2;2. TEMPOROSPATIAL PROFILE OF AXONAL DAMAGE IN MHV INFECTION;729
6.3.2.1;2.1 The relationship between demyelination and axonal damage in MHV-induced disease;730
6.3.2.2;2.2 Contribution of CD4 and CD8 cells to axonal damage;733
6.3.3;3. FUTURE DIRECTIONS;733
6.3.4;REFERENCES;734
6.4;Chapter C4 THE ROLE OF T CELLS IN CORONA-VIRUS- INDUCED DEMYELINATION;737
6.4.1;INTRODUCTION;737
6.4.2;CONCERTED ANTI-VIRAL EFFORTS OF T CELLS;738
6.4.2.1;T Cell Priming, CNS Recruitment, and Effector Function;739
6.4.2.2;Distinct Anti-Viral Functions of IFN- T and Perforin;740
6.4.2.3;Auxilliary and Direct Anti-Viral Functions of CD4 T Cells;741
6.4.3;T CELL FUNCTION DURING PERSISTENCE;742
6.4.4;T CELLS AS CORRELATES OF DEMYELINATION;743
6.4.5;CONCLUSIONS;744
6.4.6;REFERENCES;745
6.5;Chapter C5 THE ROLE OF HUMORAL IMMUNITY IN MOUSE HEPATITIS VIRUS INDUCED DEMYELINATION;748
6.5.1;HUMORAL IMMUNITY AND MULTIPLE SCLEROSIS;748
6.5.2;MHV PATHOGENESIS;750
6.5.3;HUMORAL IMMUNITY AND ACUTE INFECTION;750
6.5.4;HUMORAL IMMUNITY AND VIRAL PERSISTENCE;752
6.5.5;ANTIBODY AND DEMYELINATION;755
6.5.6;CONCLUSIONS;756
6.5.7;REFERENCES:;756
6.6;Chapter C6 THE ROLE OF T CELL EPITOPES IN CORONAVIRUS INFECTION;759
6.6.1;1. INTRODUCTION;759
6.6.2;2. CELL-MEDIATED IMMUNITY DURING MHV INFECTION OF RODENTS;760
6.6.3;3. CTL ESCAPE IN MHV-INFECTED MICE;761
6.6.4;4. BIOLOGICAL SIGNIFICANCE OF CTL ESCAPE VARIANTS IN MHV-INFECTED MICE;765
6.6.5;5. CONCLUDING REMARKS;765
6.6.6;REFERENCES.;765
6.7;Chapter C7 CORONAVIRUSES AND NEUROANTIGENS:;768
6.7.1;1. INTRODUCTION;768
6.7.2;2. NEUROANTIGENS;769
6.7.3;3. MS AND CORONAVIRUSES;770
6.7.4;4. T CELL CROSS-REACTIVITY TO CORONAVIRUS AND MYELIN PROTEINS;770
6.7.5;5. CLONAL T-CELL CROSS-REACTIVITY;772
6.7.6;6. MS SPECIFICITY OF T-CELL CROSS-REACTIVITY;773
6.7.7;7. CONCLUSIONS;774
6.7.8;ACKNOWLEDGEMENTS;775
6.7.9;REFERENCES;776
6.8;Chapter C8 CORONAVIRUS-INDUCED DEMYELINATION AND SPONTANEOUS REMYELINATION;779
6.8.1;1. INTRODUCTION;779
6.8.2;2. DISEASE SEVERITY IN THE MHV-A59 MODEL;780
6.8.3;3. MHV-A59 DISEASE SEVERITY RELATIVE TO GENDER AND ESTROUS CYCLE;783
6.8.4;4. GROWTH FACTOR EXPRESSION FOLLOWING DEMYELINATION;784
6.8.5;5. CONCLUSION;787
6.8.6;ACKNOWLEDGEMENTS;787
6.8.7;REFERENCES;787
6.9;Chapter C9 CHEMOKINES IN CORONAVIRUS-INDUCED DEMYELINATION;790
6.9.1;1. INTRODUCTION;790
6.9.2;ACKNOWLEDGEMENTS;802
6.9.3;REFERENCES;802
6.10;Chapter C10 CORONAVIRUS RECEPTORS;806
6.10.1;1. INTRODUCTION;806
6.10.2;2. RECEPTORS FOR MHV;807
6.10.3;3. INTERACTION OF CEACAM1 AND MHV S PROTEIN;811
6.10.4;4. MHV RECEPTOR AND ITS IMPLICATIONS FOR MOUSE SUSCEPTIBILITY TO MHV;812
6.10.5;5. REFERENCES;813
6.11;Chapter C11 APOPTOSIS IN MHV-INDUCED DEMYELINATION;817
6.11.1;INTRODUCTION;817
6.11.2;APOPTOSIS IN MHV-INDUCED DISEASE;818
6.11.3;DISCUSSION;819
6.11.4;ACKNOWLEDGMENTS;820
6.11.5;REFERENCES;820
6.12;Chapter C 12 THE ROLE OF METALLOPROTEINASES IN CORONA VIRUS INFECTION;822
6.12.1;INTRODUCTION;822
6.12.2;BACKGROUND;823
6.12.3;MMP AND TIMP EXPRESSION CORONAVIRUS INFECTION DURING;824
6.12.4;ROLE OF MMPS IN DEMYELINATION;826
6.12.5;CONCLUSIONS;827
6.12.6;REFERENCES;828
6.12.7;Chapter C 13 MOLECULAR DETERMINANTS OF CORONAVIRUS MHV- INDUCED DEMYELINATION;832
6.12.8;THE MHV GENOME;832
6.12.9;STRUCTURAL-FUNCTIONAL RELATIONSHIP OF MHV;833
6.12.10;THE SPIKE GLYCOPROTEIN (S);835
6.12.11;SUMMARY.;837
6.12.12;REFERENCES;838
7;Part D DEMYELINATION INDUCED BY OTHER VIRUSES;842
7.1;Chapter D1 SEMLIKI FOREST VIRUS INDUCED DEMYELINATION;843
7.1.1;1. VIRUS STRAINS;843
7.1.2;2. AGE-RELATED VIRULENCE AND RESTRICTED REPLICATION;844
7.1.3;3. ENTRY INTO AND SPREAD WITHIN THE BRAIN;845
7.1.4;4. BLOOD-BRAIN BARRIER CHANGES;846
7.1.5;5. ANTIBODY RESPONSES;847
7.1.6;6. INFLAMMATORY RESPONSES;848
7.1.7;7. NEUROPATHOLOGY;848
7.1.8;ACKNOWLEDGEMENTS;849
7.1.9;REFERENCES;849
7.2;Chapter D2 THE PATHOGENESIS OF CANINE DISTEMPER VIRUS INDUCED DEMYELINATION;853
7.2.1;1. INTRODUCTION;854
7.2.2;2. DEMYELINATING DISTEMPER ENCEPHALITIS;857
7.2.3;3. CONCLUSIONS;862
7.2.4;ACKNOWLEDGEMENTS;862
7.2.5;REFERENCES;862
8;INDEX;870