Central nervous system demyelination and remyelination in multiple sclerosis and viral models of disease

Moses Rodriguez

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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 reslted 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.

Original languageEnglish (US)
Pages (from-to)255-263
Number of pages9
JournalJournal of Neuroimmunology
Volume40
Issue number2-3
DOIs
StatePublished - 1992

Fingerprint

Theilovirus
Demyelinating Diseases
Virus Diseases
Multiple Sclerosis
Oligodendroglia
Central Nervous System
Myelin Sheath
Picornaviridae
Wounds and Injuries
Neuroglia
Axons
Immunoglobulins
Spinal Cord
Electron Microscopy
Chronic Disease
Cell Death
Monoclonal Antibodies
Viruses
T-Lymphocytes
Biopsy

Keywords

  • Immune suppression
  • Myelin
  • Oligodendrocyte
  • Picornavirus
  • Theiler's virus
  • TMEV

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Clinical Neurology
  • Neurology

Cite this

Central nervous system demyelination and remyelination in multiple sclerosis and viral models of disease. / Rodriguez, Moses.

In: Journal of Neuroimmunology, Vol. 40, No. 2-3, 1992, p. 255-263.

Research output: Contribution to journalArticle

@article{9b7bbd4b273b4f2b8c88a016b955b0e0,
title = "Central nervous system demyelination and remyelination in multiple sclerosis and viral models of disease",
abstract = "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 reslted 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.",
keywords = "Immune suppression, Myelin, Oligodendrocyte, Picornavirus, Theiler's virus, TMEV",
author = "Moses Rodriguez",
year = "1992",
doi = "10.1016/0165-5728(92)90141-7",
language = "English (US)",
volume = "40",
pages = "255--263",
journal = "Journal of Neuroimmunology",
issn = "0165-5728",
publisher = "Elsevier",
number = "2-3",

}

TY - JOUR

T1 - Central nervous system demyelination and remyelination in multiple sclerosis and viral models of disease

AU - Rodriguez, Moses

PY - 1992

Y1 - 1992

N2 - 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 reslted 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.

AB - 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 reslted 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.

KW - Immune suppression

KW - Myelin

KW - Oligodendrocyte

KW - Picornavirus

KW - Theiler's virus

KW - TMEV

UR - http://www.scopus.com/inward/record.url?scp=0026671106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026671106&partnerID=8YFLogxK

U2 - 10.1016/0165-5728(92)90141-7

DO - 10.1016/0165-5728(92)90141-7

M3 - Article

VL - 40

SP - 255

EP - 263

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

IS - 2-3

ER -