Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination

Nature Communications, 2018 · DOI: 10.1038/s41467-018-05473-1 · Published: August 2, 2018

Spinal Cord Injury Rehabilitation Regenerative Medicine & Stem Cells

Simple Explanation

Spinal cord injuries (SCI) often lead to motor, sensory, and autonomic dysfunction due to the spinal cord's limited ability to regenerate lost neurons and connections. Remyelination, the regeneration of myelin sheaths around axons, is believed to aid in functional improvements after SCI. This study investigates whether oligodendrocyte remyelination, a specific type of remyelination, is essential for spontaneous locomotor recovery following SCI. The researchers selectively ablated oligodendrocyte remyelination in transgenic mice by deleting the Myrf gene, which is crucial for oligodendrocyte differentiation. Surprisingly, the study found that despite significantly inhibited oligodendrocyte remyelination and a substantial reduction in myelinated axons, the mice exhibited unaltered spontaneous locomotor recovery. This suggests that oligodendrocyte remyelination may not be required for the initial stages of locomotor recovery after SCI.

Study Duration

6 Weeks

Participants

Transgenic mice (Myrf ICKO and controls)

Evidence Level

Level 2: Experimental study in mice

Key Findings

1
MYRF expression in PDGFRα-positive cell-derived oligodendrocytes is indispensable for myelin regeneration following contusive SCI.
2
Oligodendrocyte remyelination is not required for spontaneous recovery of stepping in mice with contusive SCI.
3
The majority of hindlimb recovery following moderate thoracic SCI occurs during the first two weeks, when little oligodendrocyte remyelination is present in mice.

Research Summary

This study investigated the role of oligodendrocyte remyelination in locomotor recovery after spinal cord injury (SCI) by selectively ablating it in transgenic mice. The researchers found that while MYRF is essential for oligodendrocyte remyelination, its absence did not alter spontaneous locomotor recovery following SCI. The findings suggest that oligodendrocyte remyelination is not a crucial component for the initial recovery of hindlimb function after contusive SCI in mice, questioning its role as a primary therapeutic target.

Practical Implications

Therapeutic Target Reassessment

The study challenges the prevailing view that remyelination is a primary target for SCI therapies, suggesting that other mechanisms may be more important for initial locomotor recovery.

Focus on Early Interventions

Since the majority of locomotor recovery occurs before significant remyelination, therapeutic strategies should prioritize interventions during the acute phase post-injury.

Further Research on Schwann Cells

Schwann cell myelination occurs early after SCI and may contribute to recovery, warranting further investigation of its role and potential as a therapeutic target.

Study Limitations

1
The study was conducted in mice, and the results may not be directly translatable to humans.
2
The specific model of contusive SCI used may not fully represent the complexity of human SCI.
3
The study focused on the initial stages of recovery, and the long-term effects of impaired remyelination were not assessed.

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