Nerve regeneration through nerve autografts after local administration of brain-derived neurotrophic factor with osmotic pumps.
OBJECTIVE
To determine whether or not administration of brain-derived neurotrophic factor (BDNF) with osmotic pumps at the site of the proximal stump of a peripheral nerve autograft can improve peripheral nerve regeneration.


METHODS
The tibialis branch of the sciatic nerve was transected and grafted with a 20-mm nerve autograft. Wistar rats (Harlan iberica, Barcelona, Spain) (n = 70) were divided into four groups: a nongrafted control group (Group I, n = 10), a grafted but nontreated control group (Group II, n = 20), a grafted saline-treated group (Group III, n = 20), and a grafted and BDNF-treated group (Group IV, n = 20). BDNF was delivered at a rate of 6 microg/day for 2 weeks after nerve repair using osmotic pumps subcutaneously implanted with a connecting tube, the distal end of which faced the proximal stump of the nerve graft. The animals were euthanized at 6 weeks. Spinal motoneurons were quantified as well as axons at the tibialis branch 5 mm distal to the distal nerve repair site. Neuron size was categorized as large (>25 microm) or small (<25 microm).


RESULTS
The statistical comparisons between the mean number of neurons in Groups II and III showed no statistical differences (P = 0.27), but there were statistically significant differences between Groups II and IV (P = 0.02) and III and IV (P = 0.02). Labeling of neurons in the group treated with BDNF represents 76% of neurons found on the nonoperated control Group I, which, in turn, is superior to the 51% of neurons found in the nontreated autograft Groups II and III. Regarding the size of motoneurons, there were no statistically significant differences between groups (P > 0.1). Finally, there were no statistically significant differences among Groups II, III, and IV regarding the number of distal axons.


CONCLUSIONS
BDNF delivered through osmotic pumps was found to have a significant capacity for improving the presence of motoneurons in the ventral spinal horn and, thus, capacity to improve nerve regeneration through nerve autografts. However, in this study, BDNF did not specifically protect against injury to motoneurons, depending on the soma size.
Hontanilla
Bernardo
B
Department of Plastic and Reconstructive Surgery, Clínica Universitaria, Universidad de Navarra, Pamplona, Spain. bhontanill@unav.es
Aubá
Cristina
C
Gorría
Oscar
O
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D004195:Disease Models, Animal; D015918:Infusion Pumps, Implantable; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000601:surgery*; D014182:Transplantation, Autologous / Q000379:methods*
D019208:Brain-Derived Neurotrophic Factor