Effects of nerve growth factor on nerve regeneration through a vein graft across a gap.

Abstract

The limited availability of donor sites for nerve grafts and their inherent associated morbidity continue to stimulate research toward finding suitable alternatives. In the following study, the effect of direct administration of nerve growth factor (NGF) into a nerve conduit across a gap was tested in a rat sciatic nerve model. A 1-cm segment of the right sciatic nerve in Sprague-Dawley rats was resected, and the gap was then bridged using one of three methods: group I (NGF-treated group, n = 12), a vein graft filled with NGF (100 ng in 0.3-ml phosphate buffered saline); group II (control group, n = 12), a vein graft filled with phosphate buffered saline only; group III (standard nerve graft, n = 11), a resected segment of the sciatic nerve. All animals were evaluated at 3 and 5 weeks by behavioral testing and at 5 weeks by electrophysiologic testing. At 3 weeks, sensory testing showed that the latency to a noxious stimulus in group I animals (8.0 +/- 5.4 sec, mean +/- SD) was significantly lower than that of group II animals (13.2 +/- 6.5 sec), indicating that sensory recovery was superior in the animals receiving NGF. The mean latency of animals in group III was 12.9 +/- 6.5 sec, but the difference between the latencies of group I and group III did not reach statistical significance. At 5 weeks, there was no difference in sensory testing between groups. Motor function in groups I and III as measured by walk pattern analysis was superior to that of group II at 5 weeks (toe spread ratios 0.66 +/- 0.09, 0.48 +/- 0.07, and 0.69 +/- 0.09 for groups I, II, and III, respectively). Mean motor conduction velocities across the 1-cm gap were 8.6 +/- 4.7 m/sec, 2.5 +/- 0.7 m/sec, and 6.9 +/- 2.9 m/sec in groups I, II, and III respectively. The difference between groups I and III was not statistically significant, but the motor conduction velocity of group II was significantly slower than that of either group I or III (p < 0.002). The positive effects of NGF on regeneration of nerves across a gap seen in this study suggest that it may be useful for treating peripheral nerve injuries in combination with autogenous vein grafts.