Function of microglia and macrophages in secondary damage after spinal cord injury

Neural Regeneration Research, 2014 · DOI: 10.4103/1673-5374.143423 · Published: October 1, 2014

Simple Explanation

Spinal cord injury (SCI) has three phases: acute, secondary and chronic. The outcomes of SCI are mainly influenced by the secondary phase. SCI causes inflammatory responses through the activation of innate immune responses that contribute to secondary injury. Macrophages in the central nervous system (CNS) derived from blood monocytes and resident microglia, are pervasive in the injured spinal cord and change their phenotypes and functions in response to signals in the lesion environment. This review discusses the behavior and influence of microglia/macrophages during secondary damage from the pathophysiology of spinal cord injury, and how microglia and macrophages affect secondary injury, and the subsets of microglia/macrophages and their interrelationships in secondary injury mechanisms.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
Inflammation, mediated by activated microglia/macrophages, plays an important role in the clearance of damaged and degenerating tissues following SCI.
2
Resident microglia and bone marrow-derived macrophages have distinct roles: microglia form a border sealing the lesion, while macrophages phagocytize apoptotic cells and clear tissue debris.
3
M1 and M2 macrophage subsets have different effects: M1 macrophages contribute to inflammation and glial scar formation, while M2 macrophages promote neuroprotection and tissue regeneration.

Research Summary

Spinal cord injury (SCI) is a devastating type of neurological trauma with limited therapeutic opportunities. The pathophysiology of SCI involves primary and secondary mechanisms of injury. Among all the secondary injury mechanisms, the inflammatory response is the major contributor and results in expansion of the lesion and further loss of neurologic function. Meanwhile, the inflammation directly and indirectly dominates the outcomes of SCI, including not only pain and motor dysfunction, but also preventingneuronal regeneration. Microglia and macrophages play very important roles in secondary injury. In this review, we focus on the roles of microglia and macrophages in secondary injury and how they contribute to the sequelae of SCI.

Practical Implications

Therapeutic Targets

Modulating macrophage function to mitigate secondary damage after SCI could lead to new therapeutic approaches.

Inflammation Management

Understanding the balance between pro-inflammatory and anti-inflammatory responses is crucial for promoting recovery of motor function.

Personalized Therapies

Targeting specific macrophage subsets based on their activities (inflammation, phagocytosis, regeneration) may optimize treatment strategies.

Study Limitations

1
Lack of specific markers to differentiate between microglia and macrophages.
2
Complexity of macrophage phenotypes and their dynamic changes in the injured spinal cord.
3
Incomplete understanding of factors driving the M1/M2 phenotype switch.

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