Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 39, Pages 10535-10545Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1903-07.2007
Keywords
gene therapy; neurotrophin; spinal cord injury; tetracycline; regulated gene expression; regeneration; Schwann cells; BDNF
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Funding
- NINDS NIH HHS [NS46466, NS09881, NS047101, NS54833] Funding Source: Medline
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Growth factors influence the topography of axonal projections during nervous system development and facilitate axonal sprouting and regeneration after injury in the adult. However, in the absence of target reinnervation and reestablishment of synaptic activity, we hypothesized that continuing delivery of neurotrophins would be required to sustain regenerating axons for prolonged times points after neurotrophin-induced axon growth after spinal cord injury ( SCI) in the adult. Using tetracycline-inducible expression of brain-derived neurotrophic factor by genetically modified fibroblasts, we were able to extensively and significantly turn growth factor expression on or off in vitro and in vivo within sites of SCI. Notably, we find that transient growth factor delivery is sufficient to sustain regenerated axons for prolonged time periods within spinal cord lesion sites. Immunohistochemical analysis demonstrated an absence of neuronal targets or synapses within transient growth factor expressing grafts but the persistent presence of Schwann cells. Thus, the adult CNS appears capable of sustaining axons that have extended after transient growth factor delivery, an effect potentially attributable to the persistence of Schwann cells in lesion/graft sites.
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