Kooperativer Bibliotheksverbund

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Format: 1 online resource (540 p.)

ISBN: 9780128007631 , 012800763X , 9780128010051 , 0128010053

Note: Description based upon print version of record. , Front Cover -- MULTIPLE SCLEROSIS: A MECHANISTIC VIEW -- Copyright -- Contents -- Contributors -- Preface -- 1 - Clinical Manifestations of Multiple Sclerosis: An Overview -- INTRODUCTION -- MOTOR AND SENSORY MANIFESTATIONS -- FATIGUE -- COGNITIVE DECLINE -- PSYCHIATRIC MANIFESTATIONS -- OPTIC NEURITIS AND OTHER NEUROOPHTHALMOLOGIC MANIFESTATIONS -- UVEITIS -- UHTHOFF PHENOMENON -- PULFRICH PHENOMENON -- BRAIN STEM INVOLVEMENT IN MS -- TRANSVERSE MYELITIS -- CEREBELLAR INVOLVEMENT AND TREMOR IN MS -- SEIZURES AND OTHER PAROXYSMAL FEATURES OF MS -- PAINFUL SYNDROMES -- BOWEL AND BLADDER DYSFUNCTION -- MOVEMENT DISORDERS -- References -- 2 - Novel Therapies for Multiple Sclerosis: A Mechanistic View -- INTRODUCTION -- LAQUINIMOD -- MONOCLONAL ANTIBODIES AS NOVEL THERAPIES FOR MS -- ALEMTUZUMAB -- DACLIZUMAB -- OCRELIZUMAB -- OFATUMUMAB -- RITUXIMAB -- THE CONCEPT OF REMYELINATION AS THERAPY FOR MS -- AntiLINGO-1 -- rHIgM22 -- References -- 3 - Role of B Cells in the Pathogenesis of Multiple Sclerosis: Mechanisms of Action -- Introduction -- EVIDENCE OF B CELL INVOLVEMENT IN THE PATHOGENESIS OF MS AND FACTORS POINTING TO THE LIMITS OF T CELL ACTION -- THE MECHANISM OF B CELL ACTION IN THE DEVELOPMENT AND PROGRESS OF MS -- THE ROLE OF CLONALLY EXPANDED B CELLS -- ROLE OF B CELLS IN PRIMING/ACTIVATING T CELLS -- REGULATORY B CELLS (BREGS) -- MEMORY B CELLS -- THE ROLE OF MHC IN TRIGGERING MS -- CONCLUSION -- LIST OF ABBREVIATIONS -- References -- 4 - Role of CD4+ T Cells in the Pathophysiology of Multiple Sclerosis -- SUMMARY -- TRADITIONAL CNS INFLAMMATION VERSUS "NEUROINFLAMMATION" -- ETIOLOGY OF MS -- PHYSIOLOGICAL AND PATHOLOGICAL ROLES OF CD4+ T CELL SUBSETS -- CLASSICAL TH1/TH2 IMMUNOREGULATORY AXIS IN MS AND ITS ANIMAL MODELS -- Role of Th1 cells -- Role of Th2 cells -- Unconventional role of Th1 and Th2 cells. , NOVEL TH17/TREG IMMUNOREGULATORY AXIS IN MS AND ITS ANIMAL MODELS -- Role of Th17 cells -- Role of Tregs -- DO "GAIN-OF-FUNCTION" CHANGES AFFECT SUSCEPTIBILITY TO MS? -- "T CELL EXHAUSTION" AS A PROTECTIVE MECHANISM AGAINST IMMUNOPATHOLOGY -- PROTECTIVE ROLES OF PD-1 AND TIM-3 IN MS AND ITS ANIMAL MODELS -- CONCLUSIONS -- Acknowledgments -- References -- 5 - Granulocyte-Macrophage Colony-Stimulating Factor in Central Nervous System Autoimmunity -- INTRODUCTION -- THE ROLE OF GM-CSF IN EAE -- GM-CSF PRODUCTION BY T CELLS IN MS -- CONCLUSION -- References -- 6 - Role of Cytokine-Mediated Crosstalk between T Cells and Nonimmune Cells in the Pathophysiology of Multiple Sclerosis -- INTRODUCTION -- PATHOGENIC ROLES OF CD4+ T CELLS -- PATHOGENIC ROLES OF CD8+ T CELLS -- T CELL SUBSETS WITH SUPPRESSIVE FUNCTIONS -- PATHOGENIC ROLE OF NONIMMUNE CELLS: THE INFLAMMATION AMPLIFIER -- THE MECHANISM OF AUTOREACTIVE T CELL INVASION INTO THE CNS -- CONCLUSION -- References -- 7 - Vitamin D: Role in Pathogenesis of Multiple Sclerosis -- INTRODUCTION -- Geoepidemiology -- Migration studies -- Vitamin D: sources -- Vitamin D: synthesis and metabolism -- Vitamin D: molecular mechanism and genetic modulation -- VITAMIN D AND GENETIC SUSCEPTIBILITY TO MS -- VITAMIN D DEFICIENCY AS A RISK FACTOR FOR MS -- Vitamin D deficiency in utero and month-of-birth effect -- Pathogenesis of MS: a T cell-mediated disease -- Mechanistic role of vitamin D in pathogenesis of MS -- Adaptive immunity: Th1, Th17, and B cells -- Role of vitamin D in maintaining peripheral immune tolerance: Tregs -- B cells and vitamin D: role in onset or propagation of disease? -- Influence of vitamin D on innate immunity: macrophages, DC, and iNKT -- EXPERIMENTAL AUTOIMMUNE ENCEPHALITIS -- ROLE OF VITAMIN D IN DISABILITY PROGRESSION AND RELAPSES IN MS -- SUPPLEMENTATION OF VITAMIN D. , THERAPEUTIC POTENTIAL OF VITAMIN D -- CLOSING REMARKS -- References -- 8 - Role of Genetic Factors in Pathophysiology of Multiple Sclerosis -- A GENETIC COMPONENT TO MULTIPLE SCLEROSIS -- IDENTIFICATION OF GENETIC RISK VARIANTS -- Human leukocyte antigen (HLA) region -- Non-HLA genes -- Linkage analysis -- Association studies -- MISSING HERITABILITY -- Additional variation -- Common risk variants -- Less common and rare variants -- Structural variation -- Epigenetics -- Underestimation of explained heritability -- Overestimating heritability -- TagSNP versus causal variant -- Interaction -- ASSOCIATION WITH DISEASE PHENOTYPE AND THERAPY OUTCOME -- Associations with individual genetic variants -- Disease course -- Age at onset -- Severity -- Gender -- Relapse -- Cerebrospinal fluid characteristics (oligoclonal bands and immunoglobulin G index) -- Brain abnormalities and cognitive function -- Response to therapy -- Cumulative burden of MS risk variants -- Genetic burden and disease phenotype -- FROM GENE TO FUNCTION -- The HLA region -- Non-HLA genetic risk variants -- Cytokine pathways -- Costimulatory molecules -- Signal transduction molecules -- Genes associated with environmental risk factors -- Genes associated with MS therapy -- Genes associated with neurodegeneration -- CONCLUDING REMARKS -- References -- 9 - Neuropathology of Multiple Sclerosis -- INTRODUCTION -- PLAQUE TYPES -- MECHANISMS OF WHITE MATTER DEMYELINATION -- THE PATHOLOGICAL SUBSTRATE OF MS PROGRESSION -- Axonal injury -- Mitochondrial injury and oxidative damage -- Iron -- Cortical pathology -- CORTICAL DEMYELINATION IN EARLY MS -- REMYELINATION -- CONCLUSION -- References -- 10 - Pathophysiology of Acute Disseminated Encephalomyelitis -- INTRODUCTION -- EPIDEMIOLOGY -- IMMUNOPATHOGENESIS OF ADEM -- Models of immunopathogenesis -- Experimental autoimmune encephalomyelitis. , Theiler's murine encephalomyelitis virus-induced demyelinating disease -- Representative human models -- Mechanisms of immune-mediated injury -- Triggers/agents associated with ADEM -- Preceding infections or vaccinations -- Host-based factors -- Genetic susceptibility -- Immune-modification -- Effector response -- Autoantibodies -- Cytokines and chemokines -- Miscellaneous markers of target organ damage -- Tau protein -- PATHOLOGY OF ADEM -- DO ADEM AND MS REPRESENT A PART OF IMMUNE-MEDIATED SPECTRUM OF DEMYELINATING DISORDERS? -- CONCLUSION -- References -- 11 - Pathophysiology of Experimental Autoimmune Encephalomyelitis -- INTRODUCTION -- EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS -- Historical perspective -- Clinical scoring of EAE -- Pathophysiology -- T cells in EAE -- Active versus passive EAE -- IMMUNOPATHOGENESIS OF EAE -- Th1 -- Th17 -- Regulatory T cells -- CD8+ T cells -- B Cells -- MONOCYTES/MACROPHAGES -- CONCLUDING REMARKS -- References -- 12 - Pathophysiology of Optic Neuritis -- INTRODUCTION -- ON IN RELATION TO THE RISK OF MS -- EPIDEMIOLOGY OF ON IN MS -- THE AFFERENT VISUAL PATHWAY -- The retina -- The optic nerve -- The optic chiasm -- The lateral geniculate nucleus (LGN) and optic radiations -- Visual cortex -- CLINICAL FEATURES OF OPTIC NEURITIS -- Patient history -- Physical examination -- Recovery -- INFLAMMATION IN OPTIC NEURITIS -- DEMYELINATION IN OPTIC NEURITIS -- AXONAL AND NEURONAL DEGENERATION IN OPTIC NEURITIS -- IMAGING AND ELECTROPHYSIOLOGIC CORRELATES OF OPTIC NEURITIS -- Optical coherence tomography (OCT) -- Magnetic resonance imaging (MRI) -- Visual evoked potentials (VEPs) -- CONCLUSIONS -- DISCLOSURES -- References -- 13 - Neurodegeneration and Remyelination in Multiple Sclerosis -- INTRODUCTION -- Mechanism of axonal damage and neurodegeneration is MS -- Reversible axonal dysfunction. , INFLAMMATION AND NEURODEGENERATION -- Lymphocytes and their soluble mediators -- Macrophages and microglia -- Astrocyte activation -- Reactive nitrogen and oxygen species -- Mitochondrial dysfunction -- Myelin loss and neurodegeneration -- Neuronal apoptosis and Wallerian degeneration -- Ion channels contributing to neurodegeneration -- Neuroprotection -- Anti-inflammatory agents -- Sodium channel blockers -- Calcium channel blockers -- Glutamate antagonists -- Nitric oxide -- Glutathione -- Erythropoietin -- Sex hormones -- Statins -- Ibudilast -- Peroxisome proliferator-activated receptor agonists -- Minocycline -- Remyelination -- Inflammation and remyelination -- Remyelination in aging -- Remyelination therapies -- Neuroregeneration -- CONCLUSION -- Further Reading -- 14 - Mechanisms of Action of Glatiramer Acetate in the Treatment of Multiple Sclerosis -- Section 1 -- INTRODUCTION -- History of experimental autoimmune/autoallergic encephalomyelitis (EAE) and myelin basic protein (MBP) -- Experimental allergic encephalomyelitis -- The development of Cop-1 -- Section 2 -- IMPACT ON ADAPTIVE IMMUNE RESPONSES -- Immunomodulatory mechanisms -- Glatiramer acetate (GA): induction of a shift from T helper (Th)1 to Th2 functional status -- Immunomodulation in the CNS -- New perspectives of GA in MS -- The role of GA activated CD8+ T cells -- The role of B Cells and natural killer (NK) cells -- Section 3 -- GLATIRAMER ACETATE AS A NEUROPROTECTIVE AGENT -- Induction of neurotrophic molecules -- Neurotrophic factors -- Impact of the innate immune system -- Studies of mechanisms of monocyte activation -- Impact of GA on monocytes/macrophages in MS and in EAE -- Prevention and reduction of CNS injury -- CONCLUSION -- References -- 15 - Mechanism of Action of Interferon Beta in Treatment of Multiple Sclerosis -- INTRODUCTION -- IFNΒ SIGNALING PATHWAY. , ASSOCIATION BETWEEN MOLECULAR DEFECTS IN IFNΒ SIGNALING AND MS PATHOGENESIS. , English

Language: English