Peptide amphiphile matrix hinders scar development after spinal cord injury

The spinal cord is a crucial component of the CNS and efforts to recovery from injuries to it mirror the kind of efforts that will be undertaken to combat injury to the brain.

Tyselling-Mattiace et al. recently analyzed the effects of peptide amphiphiline (PA) molecules that self-assemble into cylindrincal nanofibers incorporated into isoleucine-lysine-valine-alanine-valine (IKVAV), a neuroactive pentapeptide epitope, on recovery from a model of spinal cord injury in mice.The IKVAV allows the peptide amphiphiline to spontaneously assemble into nanofibers in vivo, meaning that it can be inserted as a liquid near the injury and become a tissue inside the body once it contacts cations.

This incredible technology allows for some pretty amazing results. The IKVAV PA and the control groups (glucose, sham injection, or nonbioactive PA) had liquid inserted 24 hours following the SCI injury. The IKVAV PA is present 2 weeks following injury but appears to be mostly degraded by 4 weeks.

Nine weeks later, the mice in each group were tested by the BBB locomotor scale, and the IKVAV PA group scored significantly higher than each of the other groups, which had no difference between one another. It was deemed that these numbers represented a much better recovery for the group with IKVAV PA liquid injected.

The explanation behind this recovery is a combination of many factors, including decreased aptosis, increased numbers of oligodendrocytes (these first two are clearly concurrent), decreased astroglosis (scarring), and regeneration of both motor and sensory axons.

For this last factor, mice injected with IKVAV PA had 35% of labeled corticospinal motor fibers grow through the lesion and entered the spinal cord, while no labeled fibers in the control groups were detected even 25% of the way through the lesion. This is strong evidence that the matrix of peptide amphilphile promotes the regeneration of motor axons following injury. The results were similar for the sensory axons.

The authors speculate on the mechanisms for some of this behavior, and believe that the axon regeneration may simply be a byproduct of the decreased aptosis and astroglosis, since the material has degraded before many of these changes become evident. Whatever the explanation, these self-assembling cylindrical nanofibers are a fascinating new way of conducting treatment after injury.

Reference

Tyselling-Mattiace VM, Sahni V, Niece KL, Birch D, Czeisler C, Fehlings MG, Stupp SI, Kessler JA. 2008 Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury. The Journal of Neuroscience 28: 3814-3823.  doi:10.1523/JNEUROSCI.0143-08.2008.