Preservation of neurologic function during inflammatory demyelination correlates with axon sparing in a mouse model of multiple sclerosis

D. R. Ure, M. Rodriguez

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Axonal injury has been proposed as the basis of permanent deficits in the inflammatory, demyelinating disease, multiple sclerosis. However, reports on the degree of injury are highly variable, and the responsible mechanisms are poorly understood. We examined the relationships among long-term demyelination, inflammation, axonal injury, and motor function in a model of multiple sclerosis, in which mice develop chronic, immune-mediated demyelination of the spinal cord resulting from persistent infection with Theiler's virus. We studied two strains of mice, inbred SJL/J and C57BL/6×129 mice deficient in β2-microglobulin and therefore CD8 lymphocytes. After 8 months of disease, SJL mice had considerably worse motor function than β2-microglobulin-deficient mice. Motor dysfunction correlated linearly with the extent of demyelinated lesions in the spinal cord (lesion load) within each strain, but no difference in lesion load was present between strains. Also, the extent of remyelination did not differ between strains. Instead, the disparity in motor deficits reflected differences in the integrity of descending neurons. That is, retrograde labeling of reticulospinal, vestibulospinal, and rubrospinal neurons, although reduced in all chronically diseased mice, was two to seven times higher in β2-microglobulin-deficient mice. The labeling was superior in β2-microglobulin-deficient mice despite the fact that lesion expanse and therefore the number of axons traversing lesions were similar in both strains. Thus, by all criteria axons were equivalently demyelinated in SJL and β2-microglobulin-deficient mice, but the extent of axonal injury differed significantly. These results indicate that mechanisms of demyelination and axonal injury are at least partly separable, and are consistent with the hypothesis that cytotoxic CD8 lymphocytes may selectively injure demyelinated axons. Additionally, the data suggest that axonal injury obligatorily results from chronic inflammatory demyelination and significantly contributes to neurological deficits.

Original languageEnglish (US)
Pages (from-to)399-411
Number of pages13
Issue number2
StatePublished - May 10 2002


  • Axon injury
  • CD8 lymphocytes
  • Lesions
  • Motor deficits
  • Retrograde labeling

ASJC Scopus subject areas

  • Neuroscience(all)


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