Lumbar Myeloid Cell Trafficking into Locomotor Networks after Thoracic Spinal Cord Injury

Exp Neurol, 2016 · DOI: 10.1016/j.expneurol.2016.05.019 · Published: August 1, 2016

Simple Explanation

Spinal cord injuries can cause inflammation that hinders the body's ability to repair itself. The presence of immune cells in spinal networks away from the injury site may further block functional recovery. This study examined how the spinal cord reacts to injury and how immune cells infiltrate the lumbar region, which is critical for movement. Researchers found that after a thoracic spinal cord injury (SCI), specific types of immune cells, called myeloid cells, are recruited to the lumbar region of the spinal cord, but not the cervical region. This infiltration occurs along with increases in certain chemicals that attract these cells and help them stick to blood vessels in the lumbar area. These myeloid cells change into a form of macrophage over time and their infiltration and persistence is dependent on a protein called MMP-9. Macrophage infiltration also coincides with increased inhibitory activity that impairs locomotor networks.

Study Duration

7 days

Participants

85 adult female C57BL/6J wild-type (WT) mice

Evidence Level

Not specified

Key Findings

1
Myeloid cell infiltration occurs in the lumbar cord, but not the cervical region, after thoracic SCI.
2
Infiltration of myeloid cells is associated with increased levels of chemoattractants (CCL2) and cell adhesion molecules (ICAM-1) in the lumbar vasculature.
3
MMP-9 is required for macrophage infiltration and the associated increase in inhibitory GAD67 labeling in the lumbar cord.

Research Summary

This study investigates the remote effects of thoracic spinal cord injury (SCI) on the lumbar region, focusing on myeloid cell infiltration and its impact on locomotor networks. The findings reveal that thoracic SCI induces region-specific myeloid cell recruitment into the lumbar cord, accompanied by increased chemoattractants and cell adhesion molecules. This infiltration is MMP-9 dependent and leads to enhanced GABAergic activity. The study highlights a novel injury response caudal to SCI that likely undermines recovery, suggesting that targeting remote myeloid trafficking in the lumbar cord could be a therapeutic strategy for improving outcomes after SCI.

Practical Implications

Therapeutic Target

Targeting remote myeloid trafficking in the lumbar cord could be a novel therapeutic strategy for SCI.

Personalized Rehabilitation

Evaluations of microglia vs. macrophage phenotypes may allow for personalized neurorehabilitation strategies.

Combinatorial Therapies

Optimal locomotor recovery likely depends on combinatorial therapies that unmask adaptive plasticity by reducing inflammation in the lumbar cord.

Study Limitations

1
Only female mice were used in this study, which may limit the generalizability of the findings to males.
2
The mechanism by which monocyte transvascular migration occurs into the lumbar cord while the blood spinal cord barrier appears intact is not fully understood.
3
The study focuses on early time points (24 hours and 7 days), and the long-term effects of myeloid cell infiltration on locomotor function and recovery are not fully explored.

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