Local delivery of glial cell line-derived neurotrophic factor improves facial nerve regeneration after late repair.
OBJECTIVE
Facial nerve regeneration is limited in some clinical situations: in long grafts, by aged patients, and when the delay between nerve lesion and repair is prolonged. This deficient regeneration is due to the limited number of regenerating nerve fibers, their immaturity and the unresponsiveness of Schwann cells after a long period of denervation. This study proposes to apply glial cell line-derived neurotrophic factor (GDNF) on facial nerve grafts via nerve guidance channels to improve the regeneration.


METHODS
Two situations were evaluated: immediate and delayed grafts (repair 7 months after the lesion). Each group contained three subgroups: a) graft without channel, b) graft with a channel without neurotrophic factor; and c) graft with a GDNF-releasing channel. A functional analysis was performed with clinical observation of facial nerve function, and nerve conduction study at 6 weeks. Histological analysis was performed with the count of number of myelinated fibers within the graft, and distally to the graft. Central evaluation was assessed with Fluoro-Ruby retrograde labeling and Nissl staining.


RESULTS
This study showed that GDNF allowed an increase in the number and the maturation of nerve fibers, as well as the number of retrogradely labeled neurons in delayed anastomoses. On the contrary, after immediate repair, the regenerated nerves in the presence of GDNF showed inferior results compared to the other groups.


CONCLUSIONS
GDNF is a potent neurotrophic factor to improve facial nerve regeneration in grafts performed several months after the nerve lesion. However, GDNF should not be used for immediate repair, as it possibly inhibits the nerve regeneration.
Barras
Florian M
FM
Department of Otorhinolaryngology, CHU Vaudois and University of Lausanne, Lausanne, Switzerland. florian.barras@chuv.ch
Kuntzer
Thierry
T
Zurn
Anne D
AD
Pasche
Philippe
P
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D019771:Axotomy; D005154:Facial Nerve / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000494:pharmacology; D020007:Implants, Experimental; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects*; D009431:Neural Conduction; D010784:Photomicrography; D011145:Polyvinyls; D051381:Rats; D017208:Rats, Wistar
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer