Regeneration of Corticospinal Axons into Neural Progenitor Cell Grafts After Spinal Cord Injury

Neuroscience Insights, 2020 · DOI: 10.1177/2633105520974000 · Published: October 27, 2020

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

The corticospinal tract (CST) is crucial for voluntary movement, and its injury leads to paralysis. Unlike peripheral nerves, the CST doesn't readily regenerate after spinal cord injury. However, studies show that CST axons can regenerate into neural progenitor cell (NPC) grafts placed in the injury site, suggesting that providing a supportive environment can promote regeneration. Research indicates that injury to the CST triggers intrinsic regenerative mechanisms in corticospinal neurons, challenging the previous belief that these neurons lack the capacity to regenerate.

Study Duration

Not specified

Participants

mouse, rat, and non-human primate models of spinal cord injury

Evidence Level

Commentary

Key Findings

1
Injury to the CST induces significant changes in gene expression in corticospinal neurons, indicating the activation of intrinsic regenerative mechanisms.
2
The pro-regenerative transcriptional profile in corticospinal neurons is sustained in the presence of an NPC graft, facilitating axon regeneration.
3
Huntingtin (HTT) plays a critical role in corticospinal axon regeneration, as its knockout significantly reduces regeneration.

Research Summary

Injuries to the corticospinal tract following spinal cord injury leave patients with lifelong paralysis. We have demonstrated that corticospinal neurons activate intrinsic regenerative programs in response to injury alone. Progenitor cell grafts provide an important tool to study the extrinsic and intrinsic mechanisms of successful CST regeneration

Practical Implications

Therapeutic Strategies

Understanding the molecular mechanisms underlying CST regeneration can lead to the development of targeted therapies for spinal cord injury.

NPC Graft Optimization

Identifying the specific molecules presented by NPC grafts that trigger CST regeneration can facilitate the engineering of more effective cellular or molecular grafts.

Functional Recovery Enhancement

Combining NPC grafts with rehabilitative training and electrical stimulation may further refine and optimize the rewiring of interrupted circuits, improving functional recovery.

Study Limitations

1
The complete molecular and cellular mechanisms that promote the extension of the active transcriptomic signature remain to be identified.
2
Observed corticospinal regeneration into and beyond grafts are over short gap lengths of 1 mm
3
Whether HTT overexpression might improve CST regeneration will be investigated in future studies.

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