Elevated MMP-9 in the Lumbar Cord Early after Thoracic Spinal Cord Injury Impedes Motor Relearning in Mice

The Journal of Neuroscience, 2013 · DOI: 10.1523/JNEUROSCI.1576-13.2013 · Published: August 7, 2013

Spinal Cord Injury Immunology Rehabilitation

Simple Explanation

Spinal cord injuries can cause problems far from the injury site, potentially affecting the ability to relearn movements. This study looks at the role of a protein called MMP-9 in this process. The researchers found that after a spinal cord injury in mice, MMP-9 levels increased in the lower part of the spinal cord, leading to inflammation. This inflammation seemed to interfere with the benefits of treadmill training. However, when mice without MMP-9 were given treadmill training, they showed better recovery. This suggests that MMP-9 and the inflammation it causes can hinder the spinal cord's ability to relearn movements after an injury.

Study Duration

2-9 days (early training), 35-42 days (late training)

Participants

Adult female B6.FVB(Cg)-Mmp9 tm1Tvu/J KO and C57BL/6J WT mice

Evidence Level

Not specified

Key Findings

1
MMP-9 is upregulated in the lumbar enlargement after thoracic SCI, resulting in remote inflammation during the first week after injury in C57BL/6 mice.
2
Lumbar-focused treadmill training administered during this early period impaired locomotor recovery and resulted in greater deficits in wild-type (WT) mice
3
Robust training-induced recovery occurred in MMP-9-null (KO) mice, supporting a time-sensitive adverse interaction between MMP-9 and treadmill training that influences recovery.

Research Summary

This study investigates the role of MMP-9 in remote inflammation and motor relearning after spinal cord injury (SCI) in mice. The findings demonstrate that elevated MMP-9 in the lumbar cord early after thoracic SCI impedes motor relearning, and deletion of MMP-9 promotes robust locomotor plasticity and improved recovery. The study highlights a negative, time-dependent interaction between lumbar MMP-9 production and motor relearning, suggesting that attenuating remote inflammation may be crucial for activity-dependent plasticity in locomotor interneuron networks.

Practical Implications

Therapeutic Target Identification

MMP-9 could be a potential therapeutic target to improve motor relearning after spinal cord injury by reducing remote inflammation.

Timing of Rehabilitation

The timing of rehabilitation interventions is critical, as early training in the presence of elevated MMP-9 can exacerbate deficits, while early training combined with MMP-9 reduction can promote recovery.

Combination Therapies

Combinatorial therapies that consider the interaction between spinal centric learning and remote lumbar inflammation may be more effective for recovery after SCI.

Study Limitations

1
The study was conducted on mice and may not directly translate to humans.
2
The specific mechanisms by which MMP-9 influences lumbar microglia after injury require further investigation.
3
The study focuses on a specific time window after SCI, and the long-term effects of MMP-9 inhibition need to be explored.

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