Self-assembling peptide amphiphile promotes plasticity of serotonergic fibers following spinal cord injury

J Neurosci Res, 2010 · DOI: 10.1002/jnr.22472 · Published: November 1, 2010

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

This study investigates how a self-assembling peptide amphiphile (PA) molecule, specifically one displaying the laminin epitope IKVAV, impacts recovery after spinal cord injury (SCI). The PA molecules are injected into the injured spinal cord. The research compares the effects of IKVAV-PA with a non-bioactive PA and a sham injection on the number of serotonergic fibers in the injured spinal cord. Serotonin is a neurotransmitter that can promote stepping even after complete spinal cord transection. The study also looks at the regeneration of motor and sensory axons, myelin thickness, axon number, neuron survival, and long propriospinal tract connections to understand the mechanisms behind the functional improvements seen with IKVAV-PA treatment.

Study Duration

11 weeks

Participants

Adult CD-1 female mice and Long Evans Hooded female rats

Evidence Level

Not specified

Key Findings

1
IKVAV PA injection leads to a significantly higher density of serotonergic fibers caudal to the injury site in the chronically injured spinal cord.
2
IKVAV PA injection promotes regeneration of dorsal column sensory axons in CD-1 mice, with approximately 55% of labeled axons entering the lesion in the IKVAV PA group compared to only about 18% in sham controls.
3
IKVAV PA injection resulted in significant improvement on the BBB scale compared to both the EQS PA and the sham groups.

Research Summary

This study demonstrates that injection of IKVAV-PA into the injured spinal cord consistently improves behavioral outcome in both rats and mice with different spinal cord injury models. The major potential contributors to the improved behavioral function produced by IKVAV PA treatment are the presence of serotonin caudal to the lesion as well as the confirmed regeneration of axons through the lesion. The study also found that IKVAV PA promotes regeneration of dorsal column sensory axons in CD-1 mice and that the IKVAV epitope in the IKVAV PA is essential for the effects on sensory axons after SCI.

Practical Implications

Therapeutic Potential

IKVAV-PA could be a potential therapeutic agent for SCI due to its consistent behavioral improvements across species and injury models.

Mechanism Understanding

The study highlights the importance of serotonergic fiber plasticity and axonal regeneration in SCI recovery, providing insights for future therapies.

Targeted Treatment

The necessity of the IKVAV epitope suggests the possibility of designing more targeted and effective treatments for SCI.

Study Limitations

1
The exact serotonin receptor subtype for central pattern generator modulation has not been clarified fully.
2
The study cannot determine whether the increased serotonin fibers are descending fibers that regenerated across the lesion site or local sprouting/upregulation of fibers.
3
Long propriospinal connections trended higher after IKVAV PA injection, but there were no significant differences amongst the groups.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury