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Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury
Journal article   Open access   Peer reviewed

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 and J K Lee
Neurobiology of disease, v 74, pp 114-125
Feb 2015
DOI: https://doi.org/10.1016/j.nbd.2014.10.024
PMID: 25461258
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc4323620View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Animals Axons - pathology Axons - physiology Basement Membrane - pathology Basement Membrane - physiopathology Bone Marrow Transplantation - methods Bone Morphogenetic Proteins - metabolism CD30 Ligand - metabolism Cicatrix - pathology Cicatrix - physiopathology Cicatrix - prevention & control Disease Models, Animal Female Fibroblasts - pathology Fibroblasts - physiology Macrophages - pathology Macrophages - physiology Mice, Inbred C57BL Mice, Transgenic Nerve Regeneration - physiology Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism
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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