The Prevalence and Phenotype of Activated Microglia/Macrophages within the Spinal Cord of the Hyperostotic Mouse (twy/twy) Changes in Response to Chronic Progressive Spinal Cord Compression: Implications for Human Cervical Compressive Myelopathy

PLoS ONE, 2013 · DOI: 10.1371/journal.pone.0064528 · Published: May 24, 2013

Simple Explanation

This study investigates the role of inflammation in spinal cord compression using a mouse model. The researchers focused on microglia and macrophages, which are immune cells in the spinal cord, and how their activity changes during chronic compression. The study found that as spinal cord compression worsened, there was a shift in the type of microglia/macrophages present. Initially, cells associated with repair were more prevalent, but later, cells linked to inflammation and damage increased. The findings suggest that while the body initially tries to protect the spinal cord, persistent compression leads to a harmful inflammatory response. Understanding this process could lead to new treatments for spinal cord compression in humans.

Study Duration

12, 18, and 24 weeks

Participants

twy/twy mice (n = 29 at 12, 18, 24 weeks) and control ICR mice (n = 10 in each age group)

Evidence Level

Not specified

Key Findings

1
The number of CD11b positive microglia/macrophages increased with the severity of spinal cord compression.
2
There was a shift in the polarity of M1 and M2 cells present, with the prevalence of M1 cells increasing with the severity of spinal cord compression.
3
Arginase-1-positive cells, but not iNOS-positive cells, expressed neurotrophic factors (BDNF, NGF) and higher Mac-2 immunoreactivity.

Research Summary

The study investigated chronic progressive compression of the cervical spinal cord in twy/twy mice, finding neuronal loss and increased CD11b-positive cells at the compression site. The research revealed a shift in microglia/macrophage phenotypes, from M2 (repair-associated) to M1 (inflammation-associated), with increasing compression severity. The study highlights the complex interplay of neuroprotective and neurotoxic factors in chronic spinal cord compression, suggesting potential therapeutic targets for human cervical compressive myelopathy.

Practical Implications

Therapeutic Targeting

The study suggests that targeting alternative activation of microglia/macrophages may be a viable therapeutic strategy for human CSM and OPLL.

Understanding Disease Mechanisms

The findings contribute to a better understanding of the aetiopathology of chronic spinal cord compression, which is important for developing new treatment targets in human disease.

Combined Medical Therapies

The study suggests the potential for combined medical therapies involving specific antibodies and promotion of neuronal regeneration for patients with advanced cervical compressive myelopathy.

Study Limitations

1
Limited blood cell access into the injured spinal cord in the twy/twy mouse model.
2
No evidence of the destruction of the blood spinal cord barrier.
3
Cytokines deriving from blood and having an important role in determining inflammatory and immunomodulatory activity within the spinal cord remains as a possible limitation of our animal model.

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