Cited by 199Spinal Cord Injury ResearchNerve injury and regenerationTraumatic Brain Injury and Neurovascular Disturbances

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Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury.

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Zhu, Y., Soderblom, C., Krishnan, V., Ashbaugh, J., Bethea, J.R., Lee, J.K.·2015·Neurobiology of Disease

DOI 10.1016/j.nbd.2014.10.024PMC PMC4323620

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Abstract

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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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.
ORCID: Zhu, Y.
Bethea, J.R.
Lee, J.K.
Venue: Neurobiology of Disease
Publisher: Elsevier BV
Published: 2015-02
Volume: 74
Pages: 114-125
ISSN: 0969-9961 (ISSN-L)
DOI: 10.1016/j.nbd.2014.10.024
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury.

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