Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in Cynomolgus Macaques (Macaca fasicularis)

Comparative Medicine, 2018 · DOI: · Published: February 1, 2018

Spinal Cord Injury Pharmacology Research Methodology & Design

Simple Explanation

This study presents experiments on cynomolgus macaques where traumatic spinal cord injury (TSCI) was induced using a balloon catheter inserted into the epidural space. An EMG recording device measured tail movement and muscle activity before and after TSCI. The researchers used EMG data to formulate a quantitative measure of impairment and recovery from TSCI, called the Q value. This provides a more objective measure compared to observing limb function. The study also reports histopathologic abnormalities present 90 days after the injury, valuable information because few human specimens are available at this time point due to the long-term survival of TSCI patients.

Study Duration

90-120 Days

Participants

6 adult male cynomolgus macaques

Evidence Level

Original Research

Key Findings

1
The study found that the value of Q decreased on both the left and right side immediately after the lesion in both the treatment and control groups, suggesting that the lesion led to decreased EMG activity and decreased tail movement.
2
Histopathology revealed widespread axon loss at the site of injury and in areas cephalad and caudad, as well as evidence of continuing inflammation with macrophage activation.
3
The EMG data did not demonstrate evidence of a statistically significant treatment effect from the combination of thyrotropin releasing hormone, selenium, and vitamin E.

Research Summary

This study details a non-human primate model of traumatic spinal cord injury (TSCI) in cynomolgus macaques, induced using a balloon catheter in the epidural space, focusing on tail movement impairment. EMG data was used to create a quantitative measure (Q value) for assessing impairment and recovery, and histopathological analysis was performed 90 days post-injury to evaluate tissue changes. The study found a significant decrease in Q value immediately after the lesion, indicating impaired tail movement, and identified histopathological features similar to those seen in human TSCI, though a treatment effect from TRH, selenium, and Vitamin E was not statistically significant.

Practical Implications

Improved Understanding of TSCI

The study provides valuable histopathological data at 90 days post-injury, a time point rarely available in human studies, enhancing the understanding of subacute TSCI.

Refinement of Animal Models

The use of EMG data to create a quantitative measure of impairment (Q value) can improve the objectivity and sensitivity of assessing recovery in animal models of TSCI.

Assessment of Combination Therapy Safety

The study demonstrates that the combination treatment of TRH, selenium, and vitamin E is safe in cynomolgus macaques, supporting its potential use in human clinical trials.

Study Limitations

1
The study focuses on tail movement impairment, which may not fully represent the complexities of human TSCI, particularly limb weakness and bowel/bladder dysfunction.
2
The EMG data did not show a statistically significant treatment effect, limiting the conclusions that can be drawn about the efficacy of the combination therapy.
3
The relatively small sample size (n=6) may have limited the statistical power to detect subtle treatment effects.

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