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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
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“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
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632
Basso, D., Fisher, L., Anderson, A., Jakeman, L., McTigue, D. M., & Popovich, P. (2006) · Journal of Neurotrauma · doi:10.1089/neu.2006.23.635 · Cited by 1,615
Reactive Gliosis and the Multicellular Response to CNS Damage and Disease
Burda, J. E., & Sofroniew, M. V. (2014) · Neuron · doi:10.1016/j.neuron.2013.12.034 · Cited by 1,495
Three-dimensional imaging of solvent-cleared organs using 3DISCO
Ertürk, A., Becker, K., Jährling, N., Mauch, C. P., Hojer, C. D., Egen, J. G., Hellal, F., Bradke, F., Sheng, M., & Dodt, H. (2012) · Nature Protocols · doi:10.1038/nprot.2012.119 · Cited by 997
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
Shechter, R., London, A., Varol, C., Raposo, C., Cusimano, M., Yovel, G., Rolls, A., Mack, M., Pluchino, S., Martino, G., et al. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000113 · Cited by 770
Popovich, P. G., Guan, Z., Wei, P. Y., Huitinga, I., van Rooijen, N., & Stokes, B. T. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7118 · Cited by 692
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
Perivascular Fibroblasts Form the Fibrotic Scar after Contusive Spinal Cord Injury
Soderblom, C., Luo, X., Blumenthal, E., Bray, E. R., Lyapichev, K. A., Ramos, J., Krishnan, V., Lai-Hsu, C., Park, K. K., Tsoulfas, P., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2524-13.2013 · Cited by 433
Self-citationInterleukin-6 Signaling Drives Fibrosis in Unresolved Inflammation
Fielding, C. A., Jones, G. W., McLoughlin, R. M., McLeod, L., Hammond, V. J., Fernandez, J. U., Williams, A. S., Lambie, M., Foster, T. L., Liao, C., et al. (2014) · Immunity · doi:10.1016/j.immuni.2013.10.022 · Cited by 375
Bundesen, L. Q., Scheel, T. A., Bregman, B. S., & Kromer, L. F. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-21-07789.2003 · Cited by 352
Horn, K. P., Busch, S. A., Hawthorne, A. L., van Rooijen, N., & Silver, J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2488-08.2008 · Cited by 332
Chemical Clearing and Dehydration of GFP Expressing Mouse Brains
Becker, K., Jährling, N., Saghafi, S., Weiler, R., & Dodt, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033916 · Cited by 300
Rolls, A., Shechter, R., London, A., Segev, Y., Jacob–Hirsch, J., Amariglio, N., Rechavi, G., & Schwartz, M. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050171 · Cited by 277
Kigerl, K. A., McGaughy, V. M., & Popovich, P. G. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20827 · Cited by 271
Min, K., Yang, M.-S., Kim, S. U., Jou, I., & Joe, E.-H. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3696-05.2006 · Cited by 268
Donnelly, D. J., Longbrake, E. E., Shawler, T. M., Kigerl, K. A., Lai, W., Tovar, C. A., Ransohoff, R. M., & Popovich, P. G. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2114-11.2011 · Cited by 219
Evans, T. A., Barkauskas, D. S., Myers, J., Hare, E. G., You, J., Ransohoff, R. M., Huang, A. Y.-C., & Silver, J. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.01.013 · Cited by 217
DNase I-hypersensitive sites enhance α1(I) collagen gene expression in hepatic stellate cells
Yata, Y., Scanga, A. E., Gillan, A., Yang, L., Reif, S. S., Breindl, M., Brenner, D. A., & Rippe, R. A. (2003) · Hepatology · doi:10.1053/jhep.2003.50067 · Cited by 192
IL-1 Receptor Antagonist Prevents Apoptosis and Caspase-3 Activation after Spinal Cord Injury
Nešić, O., Xu, G., McAdoo, D. J., Westlund, K. N., Hulsebosch, C. E., & Perez‐Polo, R. J. (2001) · Journal of Neurotrauma · doi:10.1089/089771501750451857 · Cited by 178
Antiangiogenic and anti-invasive effects of sunitinib on experimental human glioblastoma
de Boüard, S., Herlin, P., Christensen, J. G., Lemoisson, E., Gauduchon, P., Raymond, É., & Guillamo, J. (2007) · Neuro-Oncology · doi:10.1215/15228517-2007-024 · Cited by 175
The astrocyte/meningeal cell interface – a barrier to successful nerve regeneration?
Shearer, M. C., & Fawcett, J. W. (2001) · Cell and Tissue Research · doi:10.1007/s004410100384 · Cited by 162
Popovich, P. G., & Hickey, W. F. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.7.676 · Cited by 154
Kaplin, A. I. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25141 · Cited by 125
Microglia trigger astrocyte-mediated neuroprotection via purinergic gliotransmission
Shinozaki, Y., Nomura, M., Iwatsuki, K., Moriyama, Y., Gachet, C., & Koizumi, S. (2014) · Scientific Reports · doi:10.1038/srep04329 · Cited by 104
Blomster, L. V., Brennan, F. H., Lao, H. W., Harle, D. W., Harvey, A. R., & Ruitenberg, M. J. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.05.002 · Cited by 96
Hampton, D. W., Asher, R. A., Kondo, T., Steeves, J. D., Ramer, M. S., & Fawcett, J. W. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05940.x · Cited by 95
Activity-Induced Remodeling of Olfactory Bulb Microcircuits Revealed by Monosynaptic Tracing
Arenkiel, B. R., Hasegawa, H., Yi, J. J., Larsen, R. S., Wallace, M. L., Philpot, B. D., Wang, F., & Ehlers, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0029423 · Cited by 92
Prevention of Both Neutrophil and Monocyte Recruitment Promotes Recovery after Spinal Cord Injury
Lee, S. M., Rosen, S. D., Weinstein, P. R., van Rooijen, N., & Noble‐Haeusslein, L. J. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2011.1860 · Cited by 92
3D-reconstruction of blood vessels by ultramicroscopy
Jährling, N., Becker, K., & Dodt, H. (2009) · Organogenesis · doi:10.4161/org.5.4.10403 · Cited by 87
Haas, C., Neuhuber, B., Yamagami, T., Rao, M. S., & Fischer, I. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.11.002 · Cited by 75
Mawhinney, L., Thawer, S. G., Lu, W.-Y., van Rooijen, N., Weaver, L. C., Brown, A. M., & Dekaban, G. A. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3182479b41 · Cited by 73
Matsushita, T., Fujimoto, M., Hasegawa, M., Tanaka, C., Kumada, S., Ogawa, F., Takehara, K., & Sato, S. (2007) · PubMed · Cited by 66
Iannotti, C. A., Clark, M., Horn, K. P., van Rooijen, N., Silver, J., & Steinmetz, M. P. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.03.010 · Cited by 63
Animal models of axon regeneration after spinal cord injury
Lee, D.-H., & Lee, J. K. (2013) · Neuroscience Bulletin · doi:10.1007/s12264-013-1365-4 · Cited by 63
Self-citationLoss of Endogenous Bone Morphogenetic Protein-6 Aggravates Renal Fibrosis
Dendooven, A., van Oostrom, O., van der Giezen, D. M., Leeuwis, J. W., Snijckers, C. M. J. T., Joles, J. A., Robertson, E. J., Verhaar, M. C., Nguyen, T. Q., & Goldschmeding, R. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2010.12.005 · Cited by 59
Correction: Chemical Clearing and Dehydration of GFP Expressing Mouse Brains
Becker, K., Jährling, N., Saghafi, S., Weiler, R., & Dodt, H. (2012) · PLoS ONE · doi:10.1371/annotation/17e5ee57-fd17-40d7-a52c-fb6f86980def · Cited by 54
Fenrich, K. K., Weber, P., Rougon, G., & Debarbieux, F. C. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.256388 · Cited by 52
Lee, J. K., Johnson, C. S., & Wrathall, J. R. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.09.003 · Cited by 46
Self-citationShao, R. (2005) · World Journal of Gastroenterology · doi:10.3748/wjg.v11.i13.1995 · Cited by 44
Bone Morphogenetic Protein Signaling Protects against Cerulein-Induced Pancreatic Fibrosis
Gao, X., Cao, Y., Staloch, D. A., Gonzales, M. A., Aronson, J. F., Chao, C., Hellmich, M. R., & Ko, T. C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089114 · Cited by 32
Hasegawa, M., & Takehara, K. (2012) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2012.03.014 · Cited by 26
Ashbaugh, J. J., Brambilla, R., Karmally, S., Cabello, C., Malek, T. R., & Bethea, J. R. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203214 · Cited by 26
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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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