Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision.
Ellis-Behnke, R.G., Liang, Y.X., You, S.W., Tay, D.K.C., Zhang, S., So, K.F., and Schneider, G.E. Proc. Nat. Acad. Sci. site, 103, 5054-5059 (March 28, 2006).
Regeneration of neural tissue has posed a serious challenge to the medical and scientific communities with limited success thus far. However, an international research team reports promising results with a self-assembling peptide nanofiber scaffold (SAPNS) created from arginine, alanine, aspartate, and alanine. The scaffold, which was previously found to support synapse formation in tissue culture, was tested for its ability to permit the re-establishment of functional connections between the retina and superior colliculus after surgical transaction of the optic tract in 2-day old and young adult (8 week-old) hamsters.
The experimental protocol involved administration of 10 ul. of either SAPNS or saline into the surgical site immediately after the optic tract was severed at the level of the midbrain. Regeneration was followed via microscopic examination, histological evaluation of axonal transport of a fluorescently labeled cholera toxin subunit B (CT-B) fragment, and assessment of visually guided behavior.
Treatment with SAPNS reduced the gap created by the surgical transaction within 24 hours, regardless of the animal’s age. At 72 hours, 30 days, and 60 days post-surgery, the SAPNS-treated animals showed either further reduction in the size of the insult or complete repair. This contrasted with saline-treated animals, which showed a local inflammatory response, cell death and persistence of the tissue gap.
Results from axon tracing studies, involving use of CT-B, showed that axons in the SAPNS-treated animals re-established connections between the retina and superior colliculus. In the two-day old animals, innervation density was 78% of normal at 30 days post-treatment. Adult animals appeared “healed’’ in all cases at 30, 45, and 90 days after injury, with reinnervation being 82% of normal in the best case.
Behavioral testing of adult animals confirmed the histological results. Visual function, which was assessed by the animal’s ability to orient toward a small object, returned to 75% of normal in SAPNS-treated animals at 6 weeks post-surgery, while controls remained blind. Moreover, the treated group’s vision improved further as time passed.
This study demonstrates that nerve regeneration occurs across a self-assembling nanofiber scaffold provided shortly after a surgical insult. The results suggest that this material may serve as an alternative to autografts of peripheral nerves or other tissue for recovery from brain and spinal cord surgery. It may even also offer a therapy for CNS trauma.
Message posted by: Keith Markey
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