Remyelination protects axons from demyelination-associated axon degeneration
Abstract
In multiple sclerosis, demyelination of the CNS axons is associated with axonal injury and degeneration, which is now accepted as the major cause of neurological disability in the disease. Although the kinetics and the extent of axonal damage have been described in detail, the mechanisms by which it occurs are as yet unclear; one suggestion is failure of remyelination. The goal of this study was to test the hypothesis that failure of prompt remyelination contributes to axonal degeneration following demyelination. Remyelination was inhibited by exposing the brain to 40 Gy of X-irradiation prior to cuprizone intoxication and this resulted in a significant increase in the extent of axonal degeneration and loss compared to non-irradiated cuprizone-fed mice. To exclude the possibility that this increase was a consequence of the X-irradiation and to highlight the significance of remyelination, we restored remyelinating capacity to the X-irradiated mouse brain by transplanting of GFP-expressing embryo-derived neural progenitors. Restoring the remyelinating capacity in these mice resulted in a significant increase in axon survival compared to non-transplanted, X-irradiated cuprizone-intoxicated mice. Our results support the concept that prompt remyelination protects axons from demyelination-associated axonal loss and that remyelination failure contributes to the axon loss that occurs in multiple sclerosis.
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Remyelination is a regenerative process of the adult CNS that restores saltatory impulse conduction and trophic support to axons.
“Remyelination is a crucial regenerative process in demyelinating diseases, limiting persisting damage to the CNS. It restores saltatory nerve conduction and ensures trophic support of axons.”
From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [1]
Remyelination protects axons from ongoing degeneration.
“Remyelination is known to protect axons from ongoing degeneration [18].”
From TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis (2020) · cites this paper as [18]
Cites
Axonal transection in the lesions of multiple sclerosis
Trapp, B. D., Peterson, J., Ransohoff, R. M., Rudick, R., Mörk, S., & Bö, L. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801293380502 · Cited by 4,029 · see citing works
Wilkins, A., Majed, H., Layfield, R., Compston, A., & Chandran, S. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-12-04967.2003 · Cited by 337 · see citing works
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Remyelination in the CNS: from biology to therapy
Franklin, R. J. M., & ffrench-Constant, C. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2480 · Cited by 1,544 · see citing works
Regenerating CNS myelin — from mechanisms to experimental medicines
Franklin, R. J. M., & ffrench-Constant, C. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.136 · Cited by 647 · see citing works
Alzheimer's disease as homeostatic responses to age-related myelin breakdown
Bartzokis, G. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.08.007 · Cited by 546 · see citing works
Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging
Dal-Bianco, A., Grabner, G., Kronnerwetter, C., Weber, M., Höftberger, R., Berger, T., Auff, E., Leutmezer, F., Trattnig, S., Lassmann, H., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1636-z · Cited by 463 · see citing works
Progressive multiple sclerosis: from pathophysiology to therapeutic strategies
Faissner, S., Plemel, J. R., Gold, R., & Yong, V. W. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0035-2 · Cited by 459 · see citing works
Praet, J., Guglielmetti, C., Berneman, Z., Van der Linden, A., & Ponsaerts, P. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.10.004 · Cited by 435 · see citing works
Cignarella, F., Filipello, F., Bollman, B., Cantoni, C., Locca, A., Mikesell, R., Manis, M., Ibrahim, A., Deng, L., Benitez, B. A., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02193-z · Cited by 392 · see citing works
White matter involvement after TBI: clues to axon and myelin repair capacity
Armstrong, R. C., Mierzwa, A. J., Marion, C. M., & Sullivan, G. M. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2015.02.011 · Cited by 262 · see citing works
Cortical remyelination: A new target for repair therapies in multiple sclerosis
Chang, A., Staugaitis, S. M., Dutta, R., Batt, C. E., Easley, K. E., Chomyk, A. M., Yong, V. W., Fox, R. J., Kidd, G. J., & Trapp, B. D. (2012) · Annals of Neurology · doi:10.1002/ana.23693 · Cited by 216 · see citing works
Jelescu, I. O., Zurek, M., Winters, K. V., Veraart, J., Rajaratnam, A., Kim, N. S., Babb, J. S., Shepherd, T. M., Novikov, D. S., Kim, S. G., et al. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.02.004 · Cited by 188 · see citing works
Focal demyelination in Alzheimer’s disease and transgenic mouse models
Mitew, S., Kirkcaldie, M. T. K., Halliday, G. M., Shepherd, C. E., Vickers, J. C., & Dickson, T. C. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0657-2 · Cited by 186 · see citing works
Inhibition of CNS Remyelination by the Presence of Semaphorin 3A
Syed, Y. A., Hand, E., Möbius, W., Zhao, C., Hofer, M., Nave, K. A., & Kotter, M. R. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4930-10.2011 · Cited by 134 · see citing works
Microglia promote remyelination independent of their role in clearing myelin debris
Baaklini, C. S., Ho, M. F. S., Lange, T., Hammond, B. P., Panda, S. P., Zirngibl, M., Zia, S., Himmelsbach, K., Rana, H., Phillips, B., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113574 · Cited by 73 · see citing works
Baror, R., Neumann, B., Segel, M., Chalut, K. J., Fancy, S. P. J., Schafer, D. P., & Franklin, R. J. M. (2019) · Glia · doi:10.1002/glia.23612 · Cited by 54 · see citing works
Pentón-Rol, G., Marín-Prida, J., & Falcón-Cama, V. (2018) · Behavioral Sciences · doi:10.3390/bs8010015 · Cited by 50 · see citing works
Brain lipid binding protein (FABP7) as modulator of astrocyte function
KIPP, M., CLARNER, T., GINGELE, S., POTT, F., AMOR, S., VAN DER VALK, P., & BEYER, C. (2011) · Physiological Research · doi:10.33549/physiolres.932168 · Cited by 42 · see citing works
Zia, S., Hammond, B. P., Zirngibl, M., Sizov, A., Baaklini, C. S., Panda, S. P., Ho, M. F. S., Lee, K. V., Mainali, A., Burr, M. K., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00584-2 · Cited by 40 · see citing works
McMurran, C. E., Guzman de la Fuente, A., Penalva, R., Ben Menachem-Zidon, O., Dombrowski, Y., Falconer, J., Gonzalez, G. A., Zhao, C., Krause, F. N., Young, A. M. H., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1905787116 · Cited by 39 · see citing works
BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis
Bergner, C. G., van der Meer, F., Franz, J., Vakrakou, A., Würfel, T., Nessler, S., Schäfer, L., Nau-Gietz, C., Winkler, A., Lagumersindez-Denis, N., et al. (2025) · Brain · doi:10.1093/brain/awae293 · Cited by 16 · see citing works
- Authors
- Irvine, K. A., & Blakemore, W. F.
- Affiliations
- Multiple Sclerosis Society (GB)
- ORCID
- Irvine, K. A.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-01-29
- Volume
- 131
- Issue
- 6
- Pages
- 1464-1477
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2169924875
- Cited by
- 420
- References
- 2
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 29 · 2023: 19 · 2022: 20 · 2021: 24 · 2020: 26 · 2019: 33 · 2018: 21 · 2017: 36 · 2016: 20 · 2015: 23 · 2014: 18 · 2013: 25 · 2012: 18
- FWCI
- 18.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Multiple Sclerosis Society
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- remyelination, demyelination, axonal degeneration, multiple sclerosis, cuprizone, X-ray irradiation, axonal loss, demyelinating disease
- MeSH terms
- Animals, Axons, Corpus Callosum, Cuprizone, Demyelinating Diseases, Female, Immunohistochemistry, Mice, Inbred C57BL, Mice, Transgenic, Multiple Sclerosis, Myelin Sheath, Nerve Degeneration, Nerve Regeneration, X-Rays, Models, Animal, Stem Cell Transplantation, Diffusion Magnetic Resonance Imaging, Green Fluorescent Proteins, Mice
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