Faculty Collaboration Database

Spontaneous remyelination following extensive demyelination is associated with improved neurological function in a viral model of multiple sclerosis. Brain 2001 Jul;124(Pt 7):1403-16

Date

06/16/2001

Pubmed ID

11408335

Pubmed Central ID

PMC5455988

DOI

10.1093/brain/124.7.1403

Scopus ID

2-s2.0-0034956124 (requires institutional sign-in at Scopus site)   63 Citations

Abstract

A major question in neurobiology is whether myelin repair can restore neurological function following the course of a severe, progressive CNS demyelinating disease that induces axonal loss. In this study we used Theiler's murine encephalomyelitis virus (TMEV) to induce a chronic progressive CNS demyelinating disease in mice that was immune-mediated and pathologically similar to human multiple sclerosis. Because immunosuppression of chronically TMEV-infected mice has been shown to enhance myelin repair, we first addressed the potential roles of CD4(+) and CD8(+) T cells in the inhibition of CNS remyelination during chronic disease. TMEV infection of susceptible PL/J mice deficient in CD4(+) but not CD8(+) T cells demonstrated a significant increase in severity of pathogenesis when compared with wild-type controls. This was characterized by enhanced demyelination, spinal cord atrophy, neurological deficits, and mortality. Interestingly, the PL/J CD4(-/-) mice that survived to the chronic stage of the disease had nearly complete spontaneous myelin repair mediated by both oligodendrocytes and infiltrating Schwann cells. Therefore, we next addressed whether this spontaneous myelin repair was associated with improved neurological function despite the increased pathology. Of interest, all surviving PL/J CD4(-/-) mice showed partial restoration of motor coordination and gait that coincided temporally with spontaneous myelin repair. Furthermore, functional recovery of motor coordination correlated strongly with the percentage of myelin repair mediated by Schwann cells, whereas restoration of hindlimb gait correlated with oligodendrocyte-mediated myelin repair. This is the first study to demonstrate that spontaneous remyelination correlates with partial restoration of neurological function during the course of a progressive, immune-mediated CNS demyelinating disease. Of greater importance, functional recovery occurred despite previous severe demyelination and spinal cord atrophy.

Author List

Murray PD, McGavern DB, Sathornsumetee S, Rodriguez M

Author

Paul D. Harker-Murray MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
CD4 Antigens
CD4-Positive T-Lymphocytes
CD8 Antigens
CD8-Positive T-Lymphocytes
Cardiovirus Infections
Chronic Disease
Disease Models, Animal
Disease Progression
Mice
Mice, Knockout
Multiple Sclerosis
Myelin Sheath
Recovery of Function
Remission, Spontaneous
Severity of Illness Index
Spinal Cord
Survival Rate
Theilovirus