GDNF and NGF released by synthetic guidance channels support sciatic nerve regeneration across a long gap.
The present work was performed to determine the ability of neurotrophic factors to allow axonal regeneration across a 15-mm-long gap in the rat sciatic nerve. Synthetic nerve guidance channels slowly releasing NGF and GDNF were fabricated and sutured to the cut ends of the nerve to bridge the gap. After 7 weeks, nerve cables had formed in nine out of ten channels in both the NGF and GDNF groups, while no neuronal cables were present in the control group. The average number of myelinated axons at the midpoint of the regenerated nerves was significantly greater in the presence of GDNF than NGF (4942 +/-1627 vs. 1199 +/-431, P < or = 0.04). A significantly greater number of neuronal cells in the GDNF group, when compared to the NGF group, retrogradely transported FluoroGold injected distal to the injury site before explantation. The total number of labelled motoneurons observed in the ventral horn of the spinal cord was 98.1 +/-23.4 vs. 20.0 +/-8.5 (P < or = 0.001) in the presence of GDNF and NGF, respectively. In the dorsal root ganglia, 22.7% +/- 4.9% vs. 3.2% +/-1.9% (P +/-0.005) of sensory neurons were labelled retrogradely in the GDNF and NGF treatment groups, respectively. The present study demonstrates that, sustained delivery of GDNF and NGF to the injury site, by synthetic nerve guidance channels, allows regeneration of both sensory and motor axons over long gaps; GDNF leads to better overall regeneration in the sciatic nerve.
Fine
Eric G
EG
Division of Surgical Research and Gene Therapy Centre, CHUV, Lausanne University Medical School, Switzerland.
Decosterd
Isabelle
I
Papaloïzos
Michael
M
Zurn
Anne D
AD
Aebischer
Patrick
P
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002642:Chick Embryo; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D009414:Nerve Growth Factors; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries* / Q000601:surgery
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020932:Nerve Growth Factor