The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury.
Open accessAbstract
Spinal cord injury (SCI) leads to formation of a fibrotic scar that is inhibitory to axon regeneration. Recent evidence indicates that the fibrotic scar is formed by perivascular fibroblasts, but the mechanism by which they are recruited to the injury site is unknown. Using bone marrow transplantation in mouse model of spinal cord injury, we show that fibroblasts in the fibrotic scar are associated with hematogenous macrophages rather than microglia, which are limited to the surrounding astroglial scar. Depletion of hematogenous macrophages results in reduced fibroblast density and basal lamina formation that is associated with increased axonal growth in the fibrotic scar. Cytokine gene expression analysis after macrophage depletion indicates that decreased Tnfsf8, Tnfsf13 (tumor necrosis factor superfamily members) and increased BMP1-7 (bone morphogenetic proteins) expression may serve as anti-fibrotic mechanisms. Our study demonstrates that hematogenous macrophages are necessary for fibrotic scar formation and macrophage depletion results in changes in multiple cytokines that make the injury site less fibrotic and more conducive to axonal growth.
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“In both MCAO and SCI models, macrophages are observed in the fibrotic scar and may associate with fibroblasts”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Zhu et al., 2015
In the citing paper
“depletion of macrophages prior to SCI leads to depletion of pro-fibrotic cytokines, such as tumor necrosis factor superfamily members Tnfsf8 and Tnfsf13”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Zhu et al., 2015
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Cites
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
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Reactive Gliosis and the Multicellular Response to CNS Damage and Disease
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Three-dimensional imaging of solvent-cleared organs using 3DISCO
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Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo
Jetten, N., Verbruggen, S. E. L., Gijbels, M. J., Post, M. J., de Winther, M. P. J., & Donners, M. M. P. C. (2013) · Angiogenesis · doi:10.1007/s10456-013-9381-6 · Cited by 871
A Pericyte Origin of Spinal Cord Scar Tissue
Göritz, C., Dias, D. O., Tomilin, N., Barbacid, M., Shupliakov, O., & Frisén, J. (2011) · Science · doi:10.1126/science.1203165 · Cited by 858
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Functional regeneration beyond the glial scar
Cregg, J. M., DePaul, M. A., Filous, A. R., Lang, B. T., Tran, A. P., & Silver, J. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2013.12.024 · Cited by 686
Cited by
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Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms
Anjum, A., Yazid, M. D., Fauzi Daud, M., Idris, J., Ng, A. M. H., Selvi Naicker, A., Ismail, O. H. R., Athi Kumar, R. K., & Lokanathan, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207533 · Cited by 1,270
The Biology of Regeneration Failure and Success After Spinal Cord Injury
Tran, A. P., Warren, P. M., & Silver, J. (2018) · Physiological Reviews · doi:10.1152/physrev.00017.2017 · Cited by 896
Moving beyond the glial scar for spinal cord repair
Bradbury, E. J., & Burnside, E. R. (2019) · Nature Communications · doi:10.1038/s41467-019-11707-7 · Cited by 761
Cell biology of spinal cord injury and repair
O’Shea, T. M., Burda, J. E., & Sofroniew, M. V. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90608 · Cited by 598
Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses
Orr, M. B., & Gensel, J. C. (2018) · Neurotherapeutics · doi:10.1007/s13311-018-0631-6 · Cited by 596
Metadata
- Authors
- Zhu, Y., Soderblom, C., Krishnan, V., Ashbaugh, J., Bethea, J. R., & Lee, J. K.
- Affiliations
- University of Miami (US)
- Corresponding author
- Lee, J.K.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 74
- Pages
- 114-125
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC4323620
- OpenAlex
- W2080371301
- Cited by
- 199
- References
- 45
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 28 · 2023: 18 · 2022: 24 · 2021: 33 · 2020: 17 · 2019: 14 · 2018: 18 · 2017: 12 · 2016: 9
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NINDS (R01NS081040, R21NS082835)
- U.S. Army (W81XWH131007715)
- The Miami Project to Cure Paralysis
- the Buoniconti Fund
- Topics
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- spinal cord injury, macrophage depletion, fibrotic scar, axon regeneration, perivascular fibroblasts, bone marrow transplantation, basement membrane, tumor necrosis factor superfamily, cytokine expression, antifibrotic mechanism
- MeSH terms
- Animals, Axons, Basement Membrane, Cicatrix, Disease Models, Animal, Female, Fibroblasts, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Nerve Regeneration, Spinal Cord Injuries, Bone Marrow Transplantation, Bone Morphogenetic Proteins, CD30 Ligand, Tumor Necrosis Factor Ligand Superfamily Member 13
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