Nerve growth factor- and neurotrophin-3-releasing guidance channels promote regeneration of the transected rat dorsal root.
Dorsal roots have a limited regeneration capacity after transection. To improve nerve regeneration, the growth-promoting effects of the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were evaluated. The proteins were continuously released by synthetic nerve guidance channels bridging a 4-mm gap in the transected dorsal root. Four weeks after lesion, the regenerated nerve cables were analyzed for the presence of myelinated and unmyelinated axons. While BDNF showed a limited effect on axonal regeneration (863 +/- 39 axons/regenerated nerve, n = 6), NGF (1843 +/- 482) and NT-3 (1495 +/- 449) powerfully promoted regeneration of myelinated axons compared to channels releasing the control protein bovine serum albumin (293 +/- 39). In addition, NGF, but not BDNF nor NT-3, had a potent effect on the regeneration of unmyelinated axons (NGF, 55 +/- 1.4; BDNF, 4 +/- 0.3; NT-3, 4.7 +/- 0.3 axons/100 microm(2); n = 6). The present study suggests that synthetic nerve guidance channels slowly and continuously releasing the neurotrophins NGF and NT-3 can overcome the limited regeneration of transected dorsal root.
Bloch
J
J
Division of Surgical Research and Gene Therapy Center, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, CH-1011, Switzerland.
Fine
E G
EG
Bouche
N
N
Zurn
A D
AD
Aebischer
P
P
D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology; D002642:Chick Embryo; D003714:Denervation; D016503:Drug Delivery Systems; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000503:physiopathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009412:Nerve Fibers / Q000502:physiology / Q000648:ultrastructure; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects*; D020933:Neurotrophin 3 / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D020932:Nerve Growth Factor