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Rostrocaudal analysis of corpus callosum demyelination and axon damage across disease stages refines diffusion tensor imaging correlations with pathological features. J Neuropathol Exp Neurol 2010 Jul;69(7):704-16



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Scopus ID

2-s2.0-77954732542   124 Citations


Noninvasive assessment of the progression of axon damage is important for evaluating disease progression and developing neuroprotective interventions in multiple sclerosis patients. We examined the cellular responses correlated with diffusion tensor imaging-derived axial (lambda(parallel)) and radial (lambda(perpendicular)) 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 or astrogliosis. 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 chronic demyelination. 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.

Author List

Xie M, Tobin JE, Budde MD, Chen CI, Trinkaus K, Cross AH, McDaniel DP, Song SK, Armstrong RC


Matthew Budde PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin

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

CD11b Antigen
Corpus Callosum
Demyelinating Diseases
Diffuse Axonal Injury
Diffusion Magnetic Resonance Imaging
Disease Models, Animal
Disease Progression
Glial Fibrillary Acidic Protein
Luminescent Proteins
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Electron, Transmission
Myelin Proteins
Myelin-Associated Glycoprotein
Myelin-Oligodendrocyte Glycoprotein
Neurofilament Proteins
Statistics as Topic
Time Factors