Main description:

For several decades the unsolved etiogenetic and therapeutic problems of multiple sclerosis have offered the strongest challenge to research in neu- rology. The hope of decisive theoretical and practical progress increased when an experimental model presenting far-reaching conformity of structural and pathogenetic features was developed, namely chronic re- lapsing experimental allergic encephalomyelitis (CREAE). During the past years, Dr. Lassmann has contributed substantially to the adaptation of this model with the aim of comprehensive evaluation, thoroughly fol- lowing up his own ideas in numerous studies of individual aspects. The new possibility of continuous and detailed investigation of the clinical, morphological and immunological characteristics of temporal phase sequence of autoimmune demyelination has led to many new findings, corrections offormer hypotheses, and, from correlated studies of human multiple sclerosis, a series of important data concerning, for example, early manifestations of demyelination, the range of so-called acute mul- tiple sclerosis and the incidence of remyelination. Moreover, Dr.
Lass- mann has analysed several special problems which became definable in the course of his own studies or in collaboration with other groups, in- cluding the initial distribution of demyelinated foci, the cerebrospinal fluid phenomena and immunological findings in the nervous tissue. The results of these separate studies also led to a deeper understanding of demyelinating processes. This monograph integrates these studies and summarizes their re- sults.

Contents:

1 Introduction.- 2 The Spectram of Inflammatory Demyelinating Diseases.- 2.1 Experimental Models.- 2.2 Human Diseases.- 3 Allergic Encephalomyelitis in Humans.- 4 The Pathology of Inflammatory Demyelinating Lesions.- 4.1 Inflammatory Reaction.- 4.1.1 Inflammation in Experimental Allergic Encephalomyelitis.- 4.1.2 The Inflammatory Response in Human Inflammatory Demyelinating Diseases.- 4.2 Vascular Pathology.- 4.2.1 Vascular Pathology in EAE.- 4.2.2 Vascular Pathology in Multiple Sclerosis.- 4.3 Blood-Brain Barrier.- 4.3.1 Blood-Brain Barrier and Blood-CSF Barrier Leakage Under Physiological Conditions.- 4.3.2 The Diffusion of Proteins in the Extracellular Space of the Brain.- 4.3.3 Mechanisms and Structural Correlates of Blood- Brain Barrier Damage.- 4.3.4 The Blood-Brain Barrier in Experimental Allergic Encephalomyelitis.- 4.3.5 Implications of Blood-Brain Barrier Permeability on the Distribution of EAE Lesions Within the CNS.- 4.3.6 The Blood-Brain Barrier in Multiple Sclerosis.- 4.4 Demyelination and Myelin Degradation.- 4.4.1 Initial Stages of Demyelination in EAE.- 4.4.2 Myelin Degradation and Removal of Debris in EAE.- 4.4.3 Demyelination and Myelin Degradation in Multiple Sclerosis.- 4.5 The Fate of Oligodendroglia.- 4.5.1 Oligodendrocytes in EAE Lesions.- 4.5.2 Oligodendroglia in Multiple Sclerosis.- 4.6 Remyelination.- 4.6.1 Remyelination in Acute and Chronic EAE.- 4.6.2 Remyelination in Multiple Sclerosis.- 4.7 Sclerosis.- 4.7.1 Astroglial Reaction in the Lesions of Acute and Chronic EAE.- 4.7.2 Gliosis in Multiple Sclerosis.- 4.8 Axonal and Neuronal Pathology.- 4.8.1 Experimental Allergic Encephalomyelitis.- 4.8.2 Multiple Sclerosis.- 4.9 Meningeal Pathology.- 4.9.1 Experimental Allergic Encephalomyelitis.- 4.9.2 Multiple Sclerosis.- 4.10 Peripheral Nervous System Pathology.- 4.10.1 PNS Involvement in Different Models of Chronic EAE.- 4.10.2 Peripheral Nervous System Involvement in Multiple Sclerosis.- 4.11 Patterns of Plaque Growth.- 4.11.1 Plaque Growth in Chronic EAE.- 4.11.2 Mechanisms of Plaque Growth in Multiple Sclerosis.- 4.12 Lesional Topography in the CNS.- 4.12.1 Lesional Distribution in EAE.- 4.12.2 Lesional Topography in Human Inflammatory Demyelinating Diseases.- 4.13 The Variability of Inflammatory Demyelinating Lesions.- 4.14 EAE as a Model of Human Inflammatory Demyelinating Diseases.- 5 Immunopathogenetic Considerations.- 5.1 Transfer Studies.- 5.2 The Possible Role of Autoantigens in the Pathogenesis of Inflammatory Demyelinating Lesions.- 5.3 Conclusions.- 5.3.1 The Variability of EAE Lesions as an Expression of Multiple Antigens and Effector Mechanisms.- 5.3.2 The Compartmentalization of the Immune Reaction and Its Consequences for the Study of Chronic EAE Pathogenesis.- 5.3.3 Implications for Future Research in Human Inflammatory Demyelinating Diseases.- 6 Addendum: Material and Methods - Models of Chronic EAE.- 6.1 Material and Methods.- 6.1.1 Animal Care.- 6.1.2 Clinical Grading.- 6.1.3 Sensitization Procedure.- 6.1.4 Sampling of Animals.- 6.1.5 Human Material.- 6.2 Factors Modifying the Development of Chronic EAE Models.- 6.2.1 Guinea Pig Strains.- 6.2.2 Antigen Dose.- 6.2.3 Age of the Animals at the Time of Sensitization.- 6.2.4 Inoculation Site.- 6.2.5 Amount of Mycobacterium in the Adjuvant.- 6.2.6 Spinal Cord Subfractions.- 6.2.7 Chronic EAE in Sprague Dawley Rats.- 6.2.8 Conclusions.- 7 References.