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Cited by 175Multiple Sclerosis Research StudiesAdvanced Neuroimaging Techniques and ApplicationsNeuroinflammation and Neurodegeneration Mechanisms

Rostrocaudal Analysis of Corpus Callosum Demyelination and Axon Damage Across Disease Stages Refines Diffusion Tensor Imaging Correlations With Pathological Features

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Xie, Mingqiang, Tobin, Jennifer E., Budde, Matthew D., Chen, Chin-I, Trinkaus, Kathryn, Cross, Anne H., McDaniel, Dennis P., Song, Sheng-Kwei +1 more·2010·Journal of Neuropathology & Experimental Neurology
DOI 10.1097/nen.0b013e3181e3de90PMC PMC2901930
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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 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.

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  • Axon diameter values were reduced after 4 weeks of cuprizone and axonal atrophy persisted at 12 weeks of cuprizone treatment.

    “Xie et al. found the axon diameter values were reduced after 4 weeks of cuprizone and the axonal atrophy persisted at 12 weeks of cuprizone treatment, however, the total density of axons were not significantly different in the densities of total neurofilament profiles throughout cuprizone treatment up to 12 weeks in the corpus callosum (Xie et al. 2010).”

    From Neurite orientation dispersion and density imaging of mouse brain microstructure (2019) · cites this paper as Xie et al. 2010

  • Total density of axons was not significantly different in densities of total neurofilament profiles throughout cuprizone treatment up to 12 weeks in the corpus callosum.

    “Xie et al. found the axon diameter values were reduced after 4 weeks of cuprizone and the axonal atrophy persisted at 12 weeks of cuprizone treatment, however, the total density of axons were not significantly different in the densities of total neurofilament profiles throughout cuprizone treatment up to 12 weeks in the corpus callosum (Xie et al. 2010).”

    From Neurite orientation dispersion and density imaging of mouse brain microstructure (2019) · cites this paper as Xie et al. 2010

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  1. [1]Bruck W Inflammatory demyelination is not central to the pathogenesis of multiple sclerosis J Neurol 2005 252 Suppl 5 v10 5 16254696
  2. [2]Wilkins A Scolding N Protecting axons in multiple sclerosis Mult Scler 2008 14 1013 25 18632772
  3. [3]Kuhlmann T Lingfeld G Bitsch A Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time Brain 2002 125 2202 12 12244078
  4. [5]Pun S Santos AF Saxena S Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF Nat Neurosci 2006 9 408 19 16474388
  5. [6]Barkhof F Filippi M MRI--the perfect surrogate marker for multiple sclerosis? Nat Rev Neurol 2009 5 182 3 19347020
  6. [7]Inglese M Benedetti B Filippi M The relation between MRI measures of inflammation and neurodegeneration in multiple sclerosis J Neurol Sci 2005 233 15 9 15949493
  7. [8]Dutta R Trapp BD Pathogenesis of axonal and neuronal damage in multiple sclerosis Neurology 2007 68 S22 31 discussion S43–54 17548565
  8. [9]Alexander AL Lee JE Lazar M Diffusion tensor imaging of the corpus callosum in Autism Neuroimage 2007 34 61 73 17023185
  9. [10]Mori S Zhang J Principles of diffusion tensor imaging and its applications to basic neuroscience research Neuron 2006 51 527 39 16950152
  10. [11]Mac Donald CL Dikranian K Bayly P Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury J Neurosci 2007 27 11869 76 17978027 PMC2562788
  11. [12]Mac Donald CL Dikranian K Song SK Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury Exp Neurol 2007 205 116 31 17368446 PMC1995439
  12. [13]Song SK Sun SW Ju WK Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia Neuroimage 2003 20 1714 22 14642481
  13. [14]Sun SW Liang HF Cross AH Evolving Wallerian degeneration after transient retinal ischemia in mice characterized by diffusion tensor imaging Neuroimage 2008 40 1 10 18187343 PMC2276530
  14. [15]Sun SW Liang HF Le TQ Differential sensitivity of in vivo and ex vivo diffusion tensor imaging to evolving optic nerve injury in mice with retinal ischemia Neuroimage 2006 32 1195 204 16797189
  15. [16]DeBoy CA Zhang J Dike S High resolution diffusion tensor imaging of axonal damage in focal inflammatory and demyelinating lesions in rat spinal cord Brain 2007 130 2199 210 17557778
  16. [17]Kim JH Loy DN Liang HF Noninvasive diffusion tensor imaging of evolving white matter pathology in a mouse model of acute spinal cord injury Magn Reson Med 2007 58 253 60 17654597
  17. [18]Loy DN Kim JH Xie M Diffusion tensor imaging predicts hyperacute spinal cord injury severity J Neurotrauma 2007 24 979 90 17600514
  18. [19]Budde MD Kim JH Liang HF Toward accurate diagnosis of white matter pathology using diffusion tensor imaging Magn Reson Med 2007 57 688 95 17390365
  19. [20]Wu Q Butzkueven H Gresle M MR diffusion changes correlate with ultra-structurally defined axonal degeneration in murine optic nerve Neuroimage 2007 37 1138 47 17689104
  20. [21]Kim JH Budde MD Liang HF Detecting axon damage in spinal cord from a mouse model of multiple sclerosis Neurobiol Dis 2006 21 626 32 16298135
  21. [22]Budde MD Xie M Cross AH Axial diffusivity is the primary correlate of axonal injury in the experimental autoimmune encephalomyelitis spinal cord: A quantitative pixelwise analysis J Neurosci 2009 29 2805 13 19261876 PMC2673458
  22. [23]Song SK Yoshino J Le TQ Demyelination increases radial diffusivity in corpus callosum of mouse brain Neuroimage 2005 26 132 40 15862213
  23. [24]Sun SW Liang HF Trinkaus K Noninvasive detection of cuprizone induced axonal damage and demyelination in the mouse corpus callosum Magn Reson Med 2006 55 302 8 16408263
  24. [25]Wu QZ Yang Q Cate HS MRI identification of the rostral-caudal pattern of pathology within the corpus callosum in the cuprizone mouse model J Magn Reson Imaging 2008 27 446 53 17968901
  25. [26]Huang J Friedland RP Auchus AP Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: Preliminary evidence of axonal degeneration in the temporal lobe AJNR Am J Neuroradiol 2007 28 1943 8 17905894 PMC2426747
  26. [27]Kraus MF Susmaras T Caughlin BP White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study Brain 2007 130 2508 19 17872928
  27. [28]Schmierer K Wheeler-Kingshott CA Boulby PA Diffusion tensor imaging of post mortem multiple sclerosis brain Neuroimage 2007 35 467 77 17258908 PMC1892244
  28. [30]Lucchinetti C Bruck W Parisi J A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases Brain 1999 122 2279 95 10581222
  29. [31]Franklin KBJ Paxinos G The mouse brain in stereotaxic coordinates San Diego, CA Academic Press 1997
  30. [33]Armstrong RC Le TQ Flint NC Endogenous cell repair of chronic demyelination J Neuropathol Exp Neurol 2006 65 245 56 16651886 PMC1635791
  31. [35]McCarran WJ Goldberg MP White matter axon vulnerability to AMPA/kainate receptor-mediated ischemic injury is developmentally regulated J Neurosci 2007 27 4220 9 17429000 PMC6672529
  32. [36]Plant SR Arnett HA Ting JP Astroglial-derived lymphotoxin-alpha exacerbates inflammation and demyelination, but not remyelination Glia 2005 49 1 14 15382206
  33. [37]Feng G Mellor RH Bernstein M Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP Neuron 2000 28 41 51 11086982
  34. [38]Hiremath MM Saito Y Knapp GW Microglial/macrophage accumulation during cuprizone-induced demyelination in C57BL/6 mice J Neuroimmunol 1998 92 38 49 9916878
  35. [39]Lindner M Fokuhl J Linsmeier F Chronic toxic demyelination in the central nervous system leads to axonal damage despite remyelination Neurosci Lett 2009 453 120 5 19356606
  36. [40]Bannerman PG Hahn A Enhanced visualization of axonopathy in EAE using thy1-YFP transgenic mice J Neurol Sci 2007 260 23 32 17493638
  37. [41]Shriver LP Dittel BN T-cell-mediated disruption of the neuronal microtubule network: correlation with early reversible axonal dysfunction in acute experimental autoimmune encephalomyelitis Am J Pathol 2006 169 999 1011 16936273 PMC1698821
  38. [42]Miller DH Barkhof F Frank JA Measurement of atrophy in multiple sclerosis: Pathological basis, methodological aspects and clinical relevance Brain 2002 125 1676 95 12135961
  39. [43]Duncan ID Brower A Kondo Y Extensive remyelination of the CNS leads to functional recovery Proc Natl Acad Sci U S A 2009 106 6832 6 19342494 PMC2672502
  40. [44]Fisher E Chang A Fox RJ Imaging correlates of axonal swelling in chronic multiple sclerosis brains Ann Neurol 2007 62 219 28 17427920
  41. [45]Norris DG The effects of microscopic tissue parameters on the diffusion weighted magnetic resonance imaging experiment NMR in biomedicine 2001 14 77 93 11320535
  42. [46]Sen PN Basser PJ A model for diffusion in white matter in the brain Biophys J 2005 89 2927 38 16100258 PMC1366791
  43. [47]Hoffman PN Thompson GW Griffin JW Changes in neurofilament transport coincide temporally with alterations in the caliber of axons in regenerating motor fibers J Cell Biol 1985 101 1332 40 2413041 PMC2113909
  44. [48]Nixon RA Paskevich PA Sihag RK Phosphorylation on carboxyl terminus domains of neurofilament proteins in retinal ganglion cell neurons in vivo: influences on regional neurofilament accumulation, interneurofilament spacing, and axon caliber J Cell Biol 1994 126 1031 46 7519617 PMC2120120
  45. [49]Stidworthy MF Genoud S Suter U Quantifying the early stages of remyelination following cuprizone-induced demyelination Brain Pathol 2003 13 329 39 12946022 PMC8095752
  46. [50]Blakemore WF Remyelination of the superior cerebellar peduncle in the mouse following demyelination induced by feeding cuprizone J Neurol Sci 1973 20 73 83 4744512
  47. [51]Ludwin SK Central nervous system demyelination and remyelination in the mouse An ultrastructural study of cuprizone toxicity Lab Invest 1978 78 597 612 739762
  48. [52]Hibbits N Pannu R Wu TJ Cuprizone demyelination of the corpus callosum in mice correlates with altered social interaction and impaired sensorimotor coordination ASN Neuro 2009 1 153 64 PMC2784600 19650767
  49. [53]Irvine KA Blakemore WF Age increases axon loss associated with primary demyelination in cuprizone-induced demyelination in C57BL/6 mice J Neuroimmunol 2006 175 69 76 16626812
  50. [54]Streit WJ Walter SA Pennell NA Reactive microgliosis Prog Neurobiol 1999 57 563 81 10221782
  51. [55]Pasquini LA Calatayud CA Bertone Una AL The neurotoxic effect of cuprizone on oligodendrocytes depends on the presence of pro-inflammatory cytokines secreted by microglia Neurochem Res 2007 32 279 92 17063394
  52. [57]Crawford DK Mangiardi M Xia X Functional recovery of callosal axons following demyelination: A critical window Neuroscience 2009 164 1407 21 19800949

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Authors
Xie, M., Tobin, J. E., Budde, M. D., Chen, C.-I., Trinkaus, K., Cross, A. H., McDaniel, D. P., Song, S.-K., & Armstrong, R. C.
Affiliations
Uniformed Services University of the Health Sciences (US)
Corresponding author
Armstrong, Regina C.
ORCID
Venue
Journal of Neuropathology & Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
2010-07
Volume
69
Issue
7
Pages
704-716
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
DOI
10.1097/nen.0b013e3181e3de90
PMC
PMC2901930
OpenAlex
W2028081619
Cited by
175
References
5
Citations by year
2026: 5 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 10 · 2020: 10 · 2019: 13 · 2018: 8 · 2017: 14 · 2016: 15 · 2015: 16 · 2014: 14 · 2013: 11 · 2012: 11
FWCI
8.68
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Multiple Sclerosis Society (RG3515, RG 3670A3/2)
  • Multiple Sclerosis Society
  • National Institutes of Health (NS39293)
  • National Institute of Neurological Disorders and Stroke (R01NS047592, R01NS039293, NS39293, NS54194, NS47592, R01NS054194)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
multiple sclerosis, corpus callosum demyelination, axonal injury, cuprizone model, diffusion tensor imaging, axial diffusivity, radial diffusivity, astrocyte activation, axonal atrophy, disease stage
MeSH terms
Animals, Corpus Callosum, Cuprizone, Demyelinating Diseases, Disease Models, Animal, Glial Fibrillary Acidic Protein, Indoles, Luminescent Proteins, Macrophages, Male, Mice, Inbred C57BL, Mice, Transgenic, Myelin Proteins, Statistics as Topic, Time Factors, Neurofilament Proteins, Microglia, Disease Progression, Myelin-Associated Glycoprotein, Diffuse Axonal Injury, Diffusion Magnetic Resonance Imaging, CD11b Antigen, Microscopy, Electron, Transmission, Mice, Myelin-Oligodendrocyte Glycoprotein

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