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.

Peripheral nerve regeneration using acellular nerve grafts

“…30 Several studies have demonstrated that NGF loading into the lumen of a variety of biological and synthetic nerve grafts enhances peripheral nerve regeneration. 12,31,32 Recently, VEGF was reported to promote axonal sprouting, Schwann cell growth, and neovascularization in nerve grafts. 13,33 The number and mean diameter of axons between the grafts loaded with growth factors was higher at 1 month than the grafts loaded with saline; however, there was no difference in the later time points.…”

“…harvard.edu 12 and vascular endothelial growth factor (VEGF), 13 which are neurotrophic factors, were loaded in the acellular nerve grafts. The nerve regeneration process was analyzed histologically and by nerve function recovery assessment with electrophysiological and neurobehavioral analyses.…”

Differences in peripheral nerve degeneration/regeneration between wild‐type and neuronal nitric oxide synthase knockout mice

“…Sensory function was evaluated for each animal by measuring the latency of response to a noxious temperature stimulus (for details see Pu et al, 1999). Return of motor function was verified by observing the ability of the animals to spread their digits actively.…”

Regeneration of Primary Sensory Neurons

“…Usually the presence of Schwann cells is essential for axonal regrowth, and NGF might promote migration of Schwann cells. An autogenous vein graft filled with NGF can be a patent replacement for a donor site for nerve grafts in peripheral nerve injury and promotes recovery [48].…”