Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury

The Journal of Neuroscience, 2008 · DOI: 10.1523/JNEUROSCI.0143-08.2008 · Published: April 2, 2008

Simple Explanation

Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury (SCI). In this work, in vivo treatment with the PA after SCI reduced astrogliosis, reduced cell death, and increased the number of oligodendroglia at the site of injury. Treatment with the PA also resulted in significant behavioral improvement.

Study Duration

11 weeks

Participants

Female 129 SvJ mice (10 weeks of age)

Evidence Level

Not specified

Key Findings

1
Treatment with IKVAV PA after SCI reduced astrogliosis.
2
IKVAV PA treatment reduced cell death and increased the number of oligodendroglia at the site of injury.
3
The nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site.

Research Summary

This study demonstrates that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces. Treatment with the PA also resulted in significant behavioral improvement. The efficacy of the IKVAV PA despite the severity of the injury and delay in treatment highlights its unique ability to provide an environment conducive to recovery after SCI.

Practical Implications

Therapeutic Potential for SCI

Bioactive nanostructures can be used to inhibit glial scar formation and facilitate regeneration after SCI.

Targeted Delivery

Self-assembling nanofibers can deliver neuroactive epitopes to the spinal cord, promoting axon outgrowth.

Combination Therapies

Combining IKVAV PA with other strategies may further enhance therapeutic efficacy.

Study Limitations

1
Only partial recovery was seen, and the relationship between the behavioral improvement and the observed axon regeneration is unclear.
2
Molecular structuring of the molecule or supramolecular structuring of the nanofibers to include other bioactive sequences in addition to IKVAV or use in conjunction with other strategies may potentially further enhance its therapeutic efficacy
3
Optimization of other characteristics of the material, such as its half-life in vivo and its mechanical characteristics, may also enhance its biological activity.

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