Rostrocaudal analysis of corpus callosum demyelination and axon damage across disease stages refines diffusion tensor imaging correlations with pathological features

Mingqiang Xie, Jennifer E. Tobin, Matthew D. Budde, Chin I. Chen, Kathryn Trinkaus, Anne H. Cross, Dennis P. McDaniel, Sheng Kwei Song, Regina C. Armstrong

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Noninvasive assessment of the progression of axon damage is important for evaluating disease progression and developing neuroprotective interventions in multiple sclerosis patients. We examined thecellular responses correlated with diffusion tensor imaging-derivedaxial (λII) and radial (λ ⊥) diffusivity values throughout acute (4 weeks) and chronic (12 weeks) stages of demyelination and after 6 weeks of recovery using the cuprizone demyelination of the corpus callosum model in C57BL/6 and Thy1-YFP-16 mice. The rostrocaudal progression of pathological alterations in the corpus callosum enabled spatially and temporally defined correlations of pathological features with diffusion tensor imaging measurements. During acute demyelination, microglial/macrophage activation was most extensive and axons exhibited swellings, neurofilament dephosphorylation, and reduced diameters. Axial diffusivity values decreased in the acute phase but did not correlate with axonal atrophy during chronic demyelination. In contrast, radial diffusivity increased with the progression of demyelination but did not correlate with myelin loss orastrogliosis. Unlike other animal models with progressive neurodegeneration and axon loss, the acute axon damage did not progress to discontinuity or loss of axons even after a period of chronicdemyelination. Correlations of reversible axon pathology, demyelination, microglia/macrophage activation, and astrogliosis with regional axial and radial diffusivity measurements will facilitate the clinical application of diffusion tensor imaging in multiple sclerosis patients.

Original languageEnglish
Pages (from-to)704-716
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume69
Issue number7
DOIs
Publication statusPublished - Jul 2010
Externally publishedYes

Keywords

  • Astrogliosis
  • Axon damage
  • Corpus callosum
  • Cuprizone
  • Demyelination
  • Diffusion tensor imaging
  • Microglia activation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

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