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. CONCLUSION: 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.

Peripheral nerve regeneration through allografts compared with autografts in FK506-treated monkeys.

OBJECT: The clinical use of nerve allografts combined with immunosuppressant therapy has become a genuine possibility that could supersede the classic use of autografts. However, contradictory data have been reported on whether immunosuppressant therapy should be temporarily administered. The purpose of this study was to compare the nerve regeneration obtained using ulnar nerve allografts in nonhuman primates temporarily treated with FK506 (tacrolimus) with that obtained using nerve autografts. METHODS: Four-centimeter nerve autografts or allografts were placed in the distal ulnar motor nerve of eight monkeys. The FK506 was temporarily administered to the animals of the allograft group for 2 months. At periods of 3, 5, and 8 months postsurgery, quantitative electrophysiological recordings were obtained to estimate muscle response. A quantitative analysis of ulnar motor neurons in the spinal cord was performed and axons were counted stereologically. No statistically significant differences were found in the neuronal and axonal counts between autograft and allograft groups at 8 months. The electrophysiological studies showed no differences relative to the amplitude, but the autograft group presented with a greater nerve conduction velocity (NCV). However, no statistically significant differences were found between the number of neurons and distal axonal counts in the two groups. CONCLUSIONS: Nerve regeneration through cold-preserved allografts in a primate model temporarily treated with FK506 was similar to that obtained using nerve autografts, in terms of neuronal and axonal counts. Nevertheless, temporary immunosuppression produced lower NCV when allografts were used, with less maturation of the myelinated fibers, which indicated that a partial rejection had taken place.

Neuronal quantification in cold-preserved nerve allografts and treatment with FK-506 through osmotic pumps compared to nerve autografts.

Nerve regeneration across nerve autografts was compared to cold-preserved nerve allografts and treatment with FK-506. The tibial branch of the rat sciatic nerve was transected and immediately repaired with nerve autografts and allografts. FK-506 was administered for 4 weeks through osmotic pumps to different groups of both auto- and allograft cases. The nerves of two allografted groups were preserved with University of Wisconsin Cold Storage Solution (UWCSS) for 3 weeks. Quantification of retrograde-labelled motoneurons and axonal counts was performed. Nerve regeneration through nerve allografts treated with FK-506 or UWCSS was similar to the regeneration obtained when non-treated nerve autografts were used. However, there was no additive effect of the two treatments, and neither FK-506 nor UWCSS improved the number of gamma motoneurons. Both UWCSS and FK-506 administration with osmotic pumps was effective in improving nerve regeneration in allografts, achieving a level comparable to that obtained in non-grafted control cases.

Nerve regeneration through nerve autografts and cold preserved allografts using tacrolimus (FK506) in a facial paralysis model: a topographical and neurophysiological study in monkeys.

OBJECTIVE: Nerve regeneration through cold preserved nerve allografts is demonstrated, and treatment of nerve allografts with FK506 induces better regeneration than other immunosuppressants. We study nerve regeneration through cold preserved nerve allografts temporarily treated with FK506 and compare it with the regeneration obtained using classic nerve autografts in a facial paralysis model in monkeys. METHODS: A trunk of the facial nerve on both sides was transected in eight monkeys and immediately repaired with a 3 to 4 cm nerve autograft or allograft. FK506 was administered to the animals of the allograft group for 2 months, and nerve allografts were cold preserved for 3 weeks. At periods of 3, 5, and 8 months after surgery, quantitative electrophysiological assessment and video recordings were performed. At the end of the study, quantitative analysis of neurons in the facial nucleus was carried out, and axons were stereologically counted. RESULTS: After the regenerative period, neuronal density was higher in the autograft group. However, distal axonal counts were similar in both groups. Serial electrophysiological recordings and histology of nerve allografts showed that the grafts were partially rejected after cessation of the immunosuppressant. CONCLUSION: The regeneration through nerve allografts temporarily treated with FK506 does not achieve the electrophysiological results and neuronal counts achieved with nerve autografts, but axonal collateralization in the allografts induces a similar activation of mimic muscles.