The Origin, Fate, and Contribution of Macrophages to Spinal Cord Injury Pathology

Acta Neuropathol, 2019 · DOI: 10.1007/s00401-019-01992-3 · Published: May 1, 2019

Simple Explanation

Macrophages, derived from infiltrating monocytes, play a crucial role in spinal cord injury (SCI) by mediating inflammation, cell proliferation, tissue remodeling, and differentiation. These macrophages exhibit distinct functions from resident microglia and can exert both harmful and beneficial effects following SCI, largely influenced by environmental cues that dictate their polarization state. Different macrophage origins, such as the spleen, bone marrow, and local self-renewal, might also influence their fate and function, contributing to the complex pathobiology of SCI.

Study Duration

180 days

Participants

Not specified

Evidence Level

Not specified

Key Findings

1
Splenic macrophages are a major source of pro-inflammatory macrophages during the acute phase of SCI, while bone marrow-derived macrophages may contribute to repopulation of the injury site with anti-inflammatory macrophages.
2
Local proliferation of macrophages at the injury site may significantly contribute to the total macrophage population, suggesting that macrophage renewal may not solely depend on new monocyte influx.
3
SCI macrophages are best characterized as lipid-laden foam cells, sharing pathological mechanisms and therapeutic targets with atherosclerosis, suggesting that reducing macrophage lipid content could improve outcomes.

Research Summary

Macrophages play a central role in all phases of spinal cord injury pathogenesis, mediating both harmful and beneficial effects. The origin of macrophages, whether from the spleen, bone marrow, or local self-renewal, may influence their fate and function in SCI. Macrophage polarization states, particularly the M1/M2 spectrum and the formation of foam cells, contribute to the complex pathobiology of SCI, highlighting the need for a better understanding of macrophage identity and heterogeneity.

Practical Implications

Therapeutic Targeting of Macrophage Origins

Understanding the distinct roles of macrophages from different origins (spleen, bone marrow, local self-renewal) could lead to targeted therapies that promote beneficial macrophage populations while reducing harmful ones.

Modulation of Macrophage Polarization

Strategies aimed at shifting macrophage polarization from a pro-inflammatory (M1-like) to an anti-inflammatory (M2-like) phenotype may improve tissue repair and functional recovery after SCI.

Targeting Lipid Metabolism in Macrophages

Given the characterization of SCI macrophages as lipid-laden foam cells, targeting lipid catabolic pathways could reduce inflammation and improve outcomes, potentially drawing from therapeutic strategies used in atherosclerosis.

Study Limitations

1
The exact mechanisms governing macrophage phagocytosis after SCI, including foam cell formation, have yet to be fully elucidated.
2
The contribution of various receptors mediating myelin phagocytosis in animal models of CNS injury remains poorly understood.
3
The M1/M2 classification of macrophages is useful conceptually, but these polarization states remain elusive in vivo.

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