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The Journal of Neuroscience, September 26, 2007, 27(39):10535-10545; doi:10.1523/JNEUROSCI.1903-07.2007

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Development/Plasticity/Repair
Transient Growth Factor Delivery Sustains Regenerated Axons after Spinal Cord Injury

Armin Blesch¹ and Mark H. Tuszynski^1,2

¹Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, and ²Veterans Administration Medical Center, San Diego, California 92165

Correspondence should be addressed to Dr. Armin Blesch, Department of Neurosciences–0626, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0626. Email: ablesch{at}ucsd.edu

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.

Key words: gene therapy; neurotrophin; spinal cord injury; tetracycline; regulated gene expression; regeneration; Schwann cells; BDNF

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Received April 26, 2007; revised Aug. 9, 2007; accepted Aug. 16, 2007.

Correspondence should be addressed to Dr. Armin Blesch, Department of Neurosciences–0626, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0626. Email: ablesch{at}ucsd.edu

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