Myelin and non-myelin debris contribute to foamy macrophage formation after spinal cord injury

Neurobiol Dis, 2022 · DOI: 10.1016/j.nbd.2021.105608 · Published: February 1, 2022

Simple Explanation

After a spinal cord injury, the body's inflammatory response often persists, hindering tissue repair. Macrophages, immune cells that clear debris, can become overloaded with lipids, turning into 'foamy' macrophages. These foamy macrophages contribute to inflammation. It was believed that myelin, abundant in the spinal cord, was the primary source of these lipids. However, this study demonstrates that even without myelin, foamy macrophages still form, indicating other lipid sources are involved. The study found that foamy macrophages lacking myelin had a reduced inflammatory profile and were associated with improved outcomes after spinal cord injury in mice, suggesting that targeting these cells could be a therapeutic strategy.

Study Duration

Not specified

Participants

8-12-week-old male and female C57BL/6J mice

Evidence Level

Not specified

Key Findings

1
Foamy macrophages can form without myelin both in vitro and in vivo, suggesting that non-myelin debris contributes to foamy macrophage formation after SCI.
2
Macrophages treated with myelin-deficient spinal cord homogenate exhibited reduced expression of pro-inflammatory cytokines.
3
MBP KO mice subjected to spinal cord injury exhibited decreased lipid content, reduced immune cell infiltration, and smaller lesion sizes compared to controls.

Research Summary

This study investigates the contribution of myelin to foamy macrophage formation after spinal cord injury (SCI). The researchers found that foamy macrophages can still form without myelin, both in vitro and in vivo, indicating that other sources of lipids contribute to this pathology. The study suggests that both myelin and non-myelin sources of lipids should be considered when investigating the role of foamy macrophages in SCI and identifies the foamy macrophage assay as a platform for future mechanistic and therapeutic studies.

Practical Implications

Therapeutic Target Identification

Foamy macrophages can be targeted to mitigate inflammation and promote recovery after SCI, even in the absence of myelin. It opens avenues for further research into pharmaceutical targets.

Refined In Vitro Models

The study's novel in vitro assay, using spinal cord homogenate, provides a more physiologically relevant model for studying foamy macrophages and testing potential therapies.

Understanding Lipid Sources

Further research is needed to identify the specific non-myelin lipid sources that contribute to foamy macrophage formation and their individual roles in the inflammatory process.

Study Limitations

1
Severe motor deficits in the uninjured MBP KO mice at baseline made proper assessment of functional motor recovery after injury was not possible
2
The reason for reduced macrophage number in the MBP KO mice may be due to absence of myelin debris
3
The potential for myelin-specific effects (versus lipid content) in shaping the foamy macrophage phenotype may be attributed to the presence of myelin-related lipids (i.e. galactolipids) or protein expression (i.e. MBP itself)

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