Noninvasive detection of cuprizone induced axonal damage and demyelination in the mouse corpus callosum
Open accessAbstract
Previously, we tested the prediction that axonal damage results in decreased axial diffusivity (λ∥) while demyelination leads to increased radial diffusivity (λ⟂). Cuprizone treatment of C57BL/6 mice was a highly reproducible model of CNS white matter demyelination and remyelination affecting the corpus callosum (CC). In the present study, six C57BL/6 male mice were fed 0.2% cuprizone for 12 weeks followed by 12 weeks of recovery on normal chow. The control mice were fed normal chow and imaged in parallel. Biweekly in vivo DTI examinations showed transient decrease of λ∥ in CC at 2–6 weeks of cuprizone treatment. Immunostaining for nonphosphorylated neurofilaments demonstrated corresponding axonal damage at 4 weeks of treatment. Significant demyelination was evident from loss of Luxol fast blue staining at 6–12 weeks of cuprizone ingestion and was paralleled by increased λ⟂ values, followed by partial normalization during the remyelination phase. The sensitivity of λ⟂ to detect demyelination may be modulated in the presence of axonal damage during the early stage of demyelination at 4 weeks of cuprizone treatment. Our results suggest that λ∥ and λ⟂ may be useful in vivo surrogate markers of axonal and myelin damage in mouse CNS white matter. Magn Reson Med, 2006. Published 2006 Wiley‐Liss, Inc.
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Demyelinated areas have extensive infiltration and amplification of cells that distort the normal tissue structure in the acute demyelination cuprizone model.
“It’s reported that demyelinated areas have extensive infiltration and amplification of cells that distort the normal tissue structure in acute demyelination cuprizone model (Aggarwal et al. 2012; Sun et al. 2006).”
From Neurite orientation dispersion and density imaging of mouse brain microstructure (2019) · cites this paper as Sun et al. 2006
Axial diffusivity and radial diffusivity can be used as a noninvasive marker to probe the extent of axonal injury and myelin loss in vivo.
“Sun et al. found that axial diffusivity and radial diffusivity can be used as a noninvasive marker to probe the extent of axonal injury and myelin loss in vivo (Sun et al. 2006).”
From Neurite orientation dispersion and density imaging of mouse brain microstructure (2019) · cites this paper as Sun et al. 2006
DTI successfully detects axon and myelin injury through decreased axial diffusivity and increased radial diffusivity in animal models of CNS diseases and injuries.
“Diffusion tensor imaging (DTI) successfully detects axon and myelin injury through decreased axial diffusivity (λ∥, parallel to white matter tract) and increased radial diffusivity (λ⊥, perpendicular to white matter tract) in animal models of central nervous system (CNS) diseases and injuries (Song et al., 2002, Kim et al., 2006, Sun et al., 2006, DeBoy et al., 2007).”
From Quantifying white matter tract diffusion parameters in the presence of increased extra-fiber cellularity and vasogenic edema (2014) · cites this paper as Sun et al., 2006
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“Although the exact mechanism for the reduced in damaged axons is still not clear, the association between decreased and axonal damage has been reported (10,27,28,29).”
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- Authors
- Sun, S., Liang, H., Trinkaus, K., Cross, A. H., Armstrong, R. C., & Song, S.
- Affiliations
- Washington University in St. Louis (US)
- Uniformed Services University of the Health Sciences (US)
- Corresponding author
- Song, Sheng‐Kwei
- Venue
- Magnetic Resonance in Medicine
- Publisher
- Wiley
- Published
- 2006-01-11
- Volume
- 55
- Issue
- 2
- Pages
- 302-308
- ISSN
- 0740-3194 (ISSN-L)
- 1522-2594
- OpenAlex
- W2116547715
- Cited by
- 461
- References
- 4
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 18 · 2023: 8 · 2022: 7 · 2021: 18 · 2020: 33 · 2019: 36 · 2018: 27 · 2017: 28 · 2016: 28 · 2015: 30 · 2014: 32 · 2013: 31 · 2012: 27
- FWCI
- 17.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- onlinelibrary.wiley.com/termsAndConditions#vor (vor)
- Locations
- Magnetic Resonance in Medicine (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- Multiple Sclerosis Society
- National Institutes of Health
- National Cancer Institute (R24CA083060, R24-CA83060)
- National Institute of Neurological Disorders and Stroke (R01NS039293, NS39293)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- cuprizone, demyelination, axonal injury, corpus callosum, diffusion tensor imaging, axial diffusivity, radial diffusivity, remyelination, neurofilaments, white matter, mouse model
- MeSH terms
- Animals, Brain Chemistry, Corpus Callosum, Cuprizone, Demyelinating Diseases, Mice, Inbred C57BL, Linear Models, Statistics, Nonparametric, Diffuse Axonal Injury, Diffusion Magnetic Resonance Imaging, Mice
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