Spontaneous remyelination following extensive demyelination is associated with improved neurological function in a viral model of multiple sclerosis

P. D. Murray, D. B. McGavern, S. Sathornsumetee, Moses Rodriguez

Research output: Contribution to journalArticle

57 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1403-1416
Number of pages14
JournalBrain
Volume124
Issue number7
StatePublished - 2001

Fingerprint

Demyelinating Diseases
Myelin Sheath
Multiple Sclerosis
Theilovirus
Central Nervous System Diseases
Schwann Cells
Oligodendroglia
Gait
Atrophy
Spinal Cord
Chronic Disease
T-Lymphocytes
Neurobiology
Virus Diseases
Hindlimb
Immunosuppression
Pathology
Mortality

Keywords

  • Axonal loss
  • Glia
  • Inflammation
  • Motor function
  • Neurodegeneration
  • Picornavirus

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Spontaneous remyelination following extensive demyelination is associated with improved neurological function in a viral model of multiple sclerosis. / Murray, P. D.; McGavern, D. B.; Sathornsumetee, S.; Rodriguez, Moses.

In: Brain, Vol. 124, No. 7, 2001, p. 1403-1416.

Research output: Contribution to journalArticle

Murray, PD, McGavern, DB, Sathornsumetee, S & Rodriguez, M 2001, 'Spontaneous remyelination following extensive demyelination is associated with improved neurological function in a viral model of multiple sclerosis', Brain, vol. 124, no. 7, pp. 1403-1416.
Murray, P. D. ; McGavern, D. B. ; Sathornsumetee, S. ; Rodriguez, Moses. / Spontaneous remyelination following extensive demyelination is associated with improved neurological function in a viral model of multiple sclerosis. In: Brain. 2001 ; Vol. 124, No. 7. pp. 1403-1416.
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