STAT3 promotes corticospinal remodelling and functional recovery after spinal cord injury

EMBO reports, 2013 · DOI: 10.1038/embor.2013.117 · Published: August 9, 2013

Spinal Cord Injury Neurology Neuroplasticity

Simple Explanation

Following spinal cord injury, neurons attempt to repair their connections. This study explores the role of STAT3, a transcription factor, in this process. The study found that sustained activation of STAT3 enhances remodeling of damaged corticospinal tract (CST) fibers. Sustained STAT3 activation also leads to the creation of new connections from undamaged CST fibers. These new connections form circuits that cross the midline of the spinal cord. The formation of these new circuits improves forelimb function after spinal cord injury. This suggests that strategies to enhance remodeling could improve functional recovery after neurological damage.

Study Duration

3 weeks

Participants

Adult female C57/Bl6 mice (6–12 weeks old)

Evidence Level

Not specified

Key Findings

1
Endogenous STAT3 expression after spinal cord injury is transient and does not significantly contribute to axonal remodeling.
2
Sustained STAT3 expression, induced by viral gene transfer, enhances sprouting of lesioned CST fibers and promotes the formation of new collaterals from unlesioned CST fibers.
3
The formation of midline-crossing circuits, induced by sustained STAT3 expression, improves functional recovery after unilateral pyramidotomy.

Research Summary

The study investigates the role of STAT3 in corticospinal tract (CST) remodeling after spinal cord injury (SCI). It finds that sustained activation of STAT3 enhances remodeling of lesioned CST fibers and induces de novo formation of collaterals from unlesioned CST fibres. This recruitment of unlesioned fibers leads to the formation of midline crossing circuits that establish ipsilateral forelimb activation and functional recovery.

Practical Implications

Therapeutic Potential

Enhancing endogenous remodeling processes, such as by inducing sustained STAT3 expression, could be a promising therapeutic strategy for improving functional recovery after neurological conditions involving axon damage.

Recruitment of Unlesioned Fibers

The study highlights the potential of recruiting unlesioned fibers to the remodeling process as a means of promoting functional recovery.

Midline Crossing Circuits

The formation of midline crossing circuits is shown to contribute to improved forelimb function, suggesting that promoting their formation could be a target for therapeutic interventions.

Study Limitations

1
The viral gene transfer strategy used is not directly translatable to a clinical setting as treatment was initiated before injury.
2
The endogenous growth response of lesioned CST projection neurons is sufficient to promote the formation of detour circuits at an ‘optimal’ rate that is not improved further by the presence of more CST collaterals.
3
Not specified

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