Transient growth factor delivery sustains regenerated axons after spinal cord injury.
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.
Blesch
Armin
A
Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA. ablesch@ucsd.edu
Tuszynski
Mark H
MH
D000818:Animals; D001369:Axons / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D009416:Nerve Regeneration / Q000235:genetics*; D010957:Plasmids; D051381:Rats; D011916:Rats, Inbred F344; D012583:Schwann Cells / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D049452:Green Fluorescent Proteins; D004318:Doxycycline