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.
Keywords: Animals ; Axons/physiology/ultrastructure ; Brain-Derived Neurotrophic Factor/administration & dosage/pharmacology ; Chick Embryo ; Denervation ; Drug Delivery Systems ; Ganglia ; Spinal/ drug effects/ physiopathology/ultrastructure ; Male ; Microscopy ; Electron ; Nerve Fibers/physiology/ultrastructure ; Nerve Growth Factor/ administration & dosage/pharmacology ; Nerve Regeneration/ drug effects ; Neurotrophin 3/ administration & dosage/pharmacology ; Rats ; Rats ; Wistar ; Rats
Division of Surgical Research and Gene Therapy Center, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, CH-1011, Switzerland.
Record created on 2007-03-09, modified on 2016-08-08