Treadmill Training for Common Marmoset to Strengthen Corticospinal Connections After Thoracic Contusion Spinal Cord Injury

Frontiers in Cellular Neuroscience, 2022 · DOI: 10.3389/fncel.2022.858562 · Published: April 22, 2022

Spinal Cord Injury Neurology Rehabilitation

Simple Explanation

Spinal cord injury (SCI) can lead to locomotor dysfunction, and while rehabilitation can help lower mammals recover stepping ability, its effectiveness is limited in humans with severe SCI. This study uses a nonhuman primate model, the common marmoset, to investigate rehabilitation after severe traumatic SCI. The researchers developed a locomotor rating scale for marmosets to accurately assess their recovery of locomotor functions. Marmosets with induced paraplegia showed significant locomotor recovery after treadmill training. Kinematic analysis showed improved hindlimb stepping patterns. Intracortical microstimulation (ICMS) of the motor cortex evoked hindlimb muscle movement in the trained group, suggesting a reconnection between supraspinal input and the lumbosacral network. This primate model can be used as a preclinical test of therapies for human clinical trials.

Study Duration

11 weeks

Participants

9 common marmosets (Callithrix jacchus), female, bodyweight: 280–350 g, age: 2–5 years

Evidence Level

Not specified

Key Findings

1
Treadmill training promoted significant locomotor function recovery in marmosets with severe spinal cord injury. The trained group showed significantly higher recovery from 6 weeks after injury compared to the untrained group.
2
Kinematic analysis revealed that the stepping patterns of trained marmosets were more organized and closer to pre-injury patterns compared to untrained marmosets. This was confirmed by measuring angular movement of the hindlimb joints and principal component analysis (PCA).
3
Training-induced changes in connectivity between the motor cortex and lumbar spinal cord were observed. ICMS elicited hindlimb movement in the trained group, and the hindlimb areas on the cortical surface in the untrained group were diminished.

Research Summary

This study established a contusive spinal cord injury (SCI) model in common marmosets to investigate the effects of treadmill training on locomotor recovery. A novel Marmoset Motor Scale for Locomotion (MMS) was developed to assess locomotor functions. The results demonstrated that treadmill training significantly improved locomotor function in marmosets with severe SCI. Kinematic analysis confirmed improvements in hindlimb stepping patterns, and ICMS revealed enhanced connectivity between the motor cortex and lumbar spinal cord. Histological analysis showed that marmosets in the training group had less tissue damage and larger myelinated areas compared to the non-training group, suggesting a neuroprotective effect of rehabilitation.

Practical Implications

Preclinical Testing

The marmoset model can serve as a valuable preclinical platform for testing novel therapeutic interventions, such as pharmacological and stem cell therapies, aimed at promoting functional recovery after SCI.

Combination Therapies

The study highlights the potential of combining rehabilitation with biological repair strategies to achieve significant functional recovery after severe SCI.

Understanding Species Differences

The nonhuman primate model helps bridge the knowledge gap between rodent models and human clinical outcomes in SCI rehabilitation research.

Study Limitations

1
Small sample size
2
Lack of assessment of neurotrophic factors
3
The restoration of corticospinal connectivity did not directly indicate the sprouting and regeneration of a CST.

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