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

Y. Zhu, C. Soderblom, V. Krishnan, J. Ashbaugh, J. R. Bethea, Jae Lee

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)114-125
Number of pages12
JournalNeurobiology of Disease
Volume74
DOIs
StatePublished - Feb 1 2015

Fingerprint

Spinal Cord Injuries
Cicatrix
Macrophages
Growth
Fibroblasts
Bone Morphogenetic Protein 7
Cytokines
Wounds and Injuries
Microglia
Bone Marrow Transplantation
Basement Membrane
Axons
Regeneration
Tumor Necrosis Factor-alpha
Gene Expression

Keywords

  • Axonal growth
  • Bone morphogenetic protein
  • Fibroblasts
  • Fibrotic scar
  • Hematogenous macrophages
  • Spinal cord injury
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Neurology

Cite this

Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury. / Zhu, Y.; Soderblom, C.; Krishnan, V.; Ashbaugh, J.; Bethea, J. R.; Lee, Jae.

In: Neurobiology of Disease, Vol. 74, 01.02.2015, p. 114-125.

Research output: Contribution to journalArticle

Zhu, Y. ; Soderblom, C. ; Krishnan, V. ; Ashbaugh, J. ; Bethea, J. R. ; Lee, Jae. / Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury. In: Neurobiology of Disease. 2015 ; Vol. 74. pp. 114-125.
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