Bone Marrow-Derived Monocytes Drive the Inﬂammatory Microenvironment in Local and Remote Regions after Thoracic Spinal Cord Injury

JOURNAL OF NEUROTRAUMA, 2019 · DOI: 10.1089/neu.2018.5806 · Published: March 15, 2019

Simple Explanation

Spinal cord injuries can create a harmful inflammatory environment that hinders recovery. This study investigates how different immune cells contribute to this inflammation, particularly in areas distant from the injury site that control movement. The study found that specific immune cells called macrophages infiltrate the spinal cord after injury and express genes that promote inflammation while reducing the expression of genes that support growth and repair. The researchers also discovered that rehabilitation efforts, like treadmill training, can exacerbate the inflammatory profile of these macrophages, potentially hindering recovery. These findings suggest that controlling macrophage infiltration could improve outcomes after spinal cord injury.

Study Duration

1-7 days

Participants

Adult (3–4 months of age) female C57BL/6J wild-type (WT) mice

Evidence Level

Not specified

Key Findings

1
Macrophages are recruited to both the epicenter and lumbar cord after thoracic SCI, and they persist for at least seven days.
2
Infiltrating macrophages exhibit a pro-inflammatory gene expression profile in both the epicenter and lumbar regions, characterized by increased expression of inflammatory cytokines and chemokines and decreased expression of growth factors compared to resident microglia.
3
Acute rehabilitation exacerbates the inflammatory profile of infiltrating macrophages in the lumbar cord, suggesting a potential mechanism for the poor responses to early rehabilitation observed in some studies.

Research Summary

This study investigates the role of bone marrow-derived monocytes in the inflammatory microenvironment after thoracic spinal cord injury (SCI). The research focuses on the infiltration of peripheral myeloid cells, specifically macrophages, into both the injury epicenter and remote lumbar regions of the spinal cord. Key findings indicate that macrophages exhibit a strong pro-inflammatory profile compared to resident microglia, with elevated expression of inflammatory cytokines and chemokines and decreased expression of growth-promoting genes. Furthermore, macrophages in the lumbar cord showed heightened expression of trafficking-related genes. The study also reveals that acute rehabilitation can exacerbate the inflammatory profile of infiltrating macrophages in the lumbar cord, suggesting that limiting macrophage trafficking could be a novel therapeutic target to improve locomotion after SCI.

Practical Implications

Therapeutic Target Identification

Limiting active trafficking of macrophages into the lumbar cord identifies a novel target for SCI therapies to improve locomotion.

Rehabilitation Timing

Rehabilitation should begin once the acute inflammatory response has subsided and macrophages have decreased their inflammatory profile.

Understanding Below-Level Deficits

The impact of macrophages in altering the lumbar microenvironment may have large implications for below-level deficits.

Study Limitations

1
Long-term consequences of peripherally derived macrophages in the lumbar cord still needs to be explored.
2
Macrophage proﬁles were determined at seven days after SCI and acutely after intervention.
3
The study focused primarily on gene expression and cellular changes, with less emphasis on direct functional outcomes in response to specific interventions.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury