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  4. Modulation of Extrinsic and Intrinsic Signaling Together with Neuronal Activation Enhances Forelimb Motor Recovery after Cervical Spinal Cord Injury

Modulation of Extrinsic and Intrinsic Signaling Together with Neuronal Activation Enhances Forelimb Motor Recovery after Cervical Spinal Cord Injury

eNeuro, 2025 · DOI: https://doi.org/10.1523/ENEURO.0359-24.2025 · Published: March 1, 2025

Spinal Cord InjuryNeurology

Simple Explanation

This study explores a new approach to improve motor recovery after spinal cord injury (SCI) by combining two strategies: modifying certain factors in nerve cells and stimulating those nerve cells. The researchers modified corticospinal neurons (CSNs) by deleting RhoA and Pten, which are known to prevent nerve regeneration. They also used chemogenetic stimulation to activate these modified neurons. The results showed that this combined approach led to better nerve growth and improved motor function in mice with SCI compared to using either strategy alone, suggesting potential for more effective SCI treatments.

Study Duration
Not specified
Participants
Mice
Evidence Level
Not specified

Key Findings

  • 1
    The combination of RhoA/Pten deletion in corticospinal neurons (CSNs) with chemogenetic neuronal stimulation promotes greater axonal growth and presynaptic bouton formation in CSNs within the spinal cord compared with RhoA;Pten deletion alone.
  • 2
    Chemogenetic neuronal stimulation of RhoA;Pten-deleted CSNs improves forelimb performance in behavioral tasks after SCI compared with RhoA;Pten deletion alone.
  • 3
    The synergistic effects of genetic deletion of RhoA;Pten and CSN stimulation limited axon dieback and promoted presynaptic growth in CSN axons at and below the site of injury.

Research Summary

The study investigates whether combining RhoA;Pten deletion in corticospinal neurons (CSNs) with chemogenetic neuronal stimulation synergistically enhances CS circuit rewiring and forelimb functional recovery after cervical SCI in mice. Results demonstrate that the combinatorial intervention spurred CS axon regrowth and achieved partial restoration of forelimb motor recovery. The study suggests that combinatorial treatment strategies, specifically tailored to the needs of individual patients, will maximize motor recovery in those impacted by traumatic SCI.

Practical Implications

Enhanced Axonal Growth

Combining genetic modifications with neuronal stimulation can significantly enhance axonal growth after SCI.

Improved Motor Recovery

The combinatorial approach leads to improved forelimb motor performance compared to individual strategies.

Personalized Treatment

Tailoring treatment strategies to the specific needs of individual SCI patients may maximize motor recovery.

Study Limitations

  • 1
    Fluorescence intensity was used as a surrogate measure for axon number, which may be influenced by variations in viral injection efficiency or experimental conditions.
  • 2
    Limited axon regrowth observed following SCI may be insufficient for regaining preinjury levels of motor control.
  • 3
    Continuous administration of hM3Dq may result in its downregulation, which would lower the activation of CSNs.

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