Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 14, Pages 3814-3823Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0143-08.2008
Keywords
spinal cord injury; nanotechnology; gliosis; regeneration; extracellular matrix; functional recovery
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Funding
- NIBIB NIH HHS [R01 EB003806-01, R01 EB003806] Funding Source: Medline
- NINDS NIH HHS [R01 NS20013-21, P50 NS054287, R01 NS020778-24, R01 NS020013, R01 NS020778, P50 NS54287] Funding Source: Medline
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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). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created within the extracellular spaces of the spinal cord by simply injecting a liquid. The molecules are designed to form cylindrical nanofibers that display to cells in the spinal cord the laminin epitope IKVAV at nearly van der Waals density. IKVAV PA nanofibers are known to inhibit glial differentiation of cultured neural stem cells and to promote neurite outgrowth from cultured neurons. 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. Furthermore, the nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site. Treatment with the PA also resulted in significant behavioral improvement. These observations demonstrate 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.
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