A Cervical Hemi-Contusion Spinal Cord Injury Model for the Investigation of Novel Therapeutics Targeting Proximal and Distal Forelimb Functional Recovery

JOURNAL OF NEUROTRAUMA, 2015 · DOI: 10.1089/neu.2014.3792 · Published: December 15, 2015

Spinal Cord Injury Neurology Research Methodology & Design

Simple Explanation

This study presents a refined animal model for cervical spinal cord injury, closely mimicking the injuries seen in humans. The model uses a device to create controlled contusions on the spinal cord of rats at the C4 level. The severity of the injury is graded by controlling the displacement of the spinal cord, creating either a moderate (0.6 mm) or large (0.8 mm) injury. Researchers then observed the rats for 12 weeks, assessing their recovery of both proximal and distal forelimb functions using a variety of behavioral tests. The results showed that the model produces consistent and graded injuries, with the larger injuries causing more severe and lasting deficits in both proximal and distal upper limb function. The model is valuable for testing new treatments aimed at improving forelimb functional recovery after spinal cord injury.

Study Duration

12 weeks

Participants

23 female Long Evans rats

Evidence Level

Not specified

Key Findings

1
Moderate (0.6 mm) and large (0.8 mm) displacement injuries showed consistent differences in forelimb asymmetry, metrics of the CatWalk, and sub-scores of the IBB.
2
Long lasting proximal and distal upper limb deficits followed the 0.8 mm injury, while transient proximal with prolonged distal limb deficits followed the 0.6 mm injury.
3
Significant differences in loss of ipsilateral unmyelinated and myelinated white matter was detected between injury severities.

Research Summary

The study updates and characterizes an electromagnetic spinal cord injury device (ESCID) to create consistent C4 hemi-contusion injuries in rats, graded by displacement (0.6 mm or 0.8 mm). Behavioral assessments over 12 weeks revealed that the 0.8 mm injury resulted in long-term proximal and distal forelimb deficits, while the 0.6 mm injury led to transient proximal and prolonged distal deficits. Histological analysis showed significant differences in ipsilateral white matter myelination between the injury groups, suggesting that spared myelinated fibers contribute to the observed behavioral differences.

Practical Implications

Therapeutic target identification

The model can be used to identify therapeutic targets for enhancing axonal growth, plasticity, or myelination of spared pathways.

Treatment testing

The model is suitable for testing novel treatments aimed at improving both proximal and distal upper limb functions after cervical SCI.

Understanding recovery mechanisms

The model can help elucidate the mechanisms of spontaneous recovery and the role of spared tissue in mediating functional improvements.

Study Limitations

1
The forelimb asymmetry use task did not resolve the different injury magnitudes.
2
Gray matter is secondarily affected in rodent contusion spinal cord injuries compared with white matter.
3
To quantify total motoneuron number optical fractionator method is required.

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