Central nervous system demyelination and remyelination in multiple sclerosis and viral models of disease.
The mechanisms of myelin injury and repair were studied in acute multiple sclerosis lesions and in a murine model of demyelination induced by a virus. Injury to oligodendrocytes resulting in degeneration of inner glial loops and inner myelin lamellae (dying-back oligodendrogliopathy) was observed by electron microscopy in brain biopsies of acute demyelinating lesions. Attempts at central nervous system remyelination as manifested by thinly myelinated axons and proliferation of oligodendrocytes were observed at the edge of many acute plaques. To develop therapeutic strategies to inhibit demyelination or promote remyelination, mice infected intracranially with Theiler's virus (a picornavirus) were studied. Experimental manipulation of Theiler's virus-infected mice by treatment during chronic demyelinating disease with immunoglobulins directed at normal spinal cord antigens or with monoclonal antibodies which deplete CD4 or CD8-positive T cells resulted in augmentation of new myelin synthesis. These observations suggest that disturbances in the myelinating function of oligodendrocytes, events not accompanied by death of these cells, may be among the earliest pathological events in multiple sclerosis. Experiments using the Theiler's virus model of demyelination indicate that manipulation of the immune response has the potential to promote central nervous system remyelination and functional recovery in multiple sclerosis.
Rodriguez
M
M
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
D000818:Animals; D002493:Central Nervous System Diseases / Q000503:physiopathology*; D003711:Demyelinating Diseases / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology; D007165:Immunosuppression Therapy; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D009186:Myelin Sheath / Q000502:physiology*; D009422:Nervous System Diseases / Q000382:microbiology* / Q000503:physiopathology; D011859:Radiography; D013601:T-Lymphocytes / Q000502:physiology; D014777:Virus Diseases
D007136:Immunoglobulins