Skarupa D and Kalliainen LK. Department of Surgery, Division of Plastic Surgery, Ohio State University, 325-B North Means Hall, 1654 Upham Drive, Columbus, OH, USA
Background: Nerve grafts are an imperfect solution to cross large nerve gaps, but there are limited alternatives. Incomplete sensory-motor recovery is associated with loss of Schwann cells, central graft necrosis, fascicular mismatch, and pruning of nerve fibers. Graft revascularization is a necessary precedent for axon ingrowth. Vascular endothelial growth factor (VEGF) is angiogenic as well as neuroprotective and stimulates Schwann cell growth and neovascularization of acellular nerve grafts. Chronic electrical stimulation of skeletal muscle upregulates VEGF expression. Brief electrical stimulation was shown to promote motor axon regeneration in the rat, but the mechanism behind this was not investigated. Purpose: The long-term objective is to improve the outcome of nerve injuries by optimizing nerve growth across a graft. The specific aims of this study were 1) to evaluate the effect of intraoperative nerve stimulation on VEGF expression in the spinal cord, in nerve grafts, and in skeletal muscle in the rat hindlimb; and 2) to investigate the effects of electrical stimulation of the sciatic nerve on reinnervation of skeletal muscle. Methods: Twenty young adult rats underwent resection of a segment of the proximal peroneal nerve with reversal and immediate repair to model a nerve graft. In the control group, electrodes were placed on the proximal nerve stump for one hour, but no electrical stimulus was applied. In the experimental group, an electrical stimulus was applied to the proximal nerve stump for one hour after graft coaptation. Nerves were stimulated with square wave pulses delivered at 2-3V, 100 microsec, and 10Hz. After four weeks of recovery, the animals were euthanized, and tissue was harvested for fiber counting and immunohistochemical analysis. The extensor digitorum longus muscle was weighed and snap frozen. The sections are being stained for VEGF as described above and for neural cell adhesion molecule, a marker of denervated muscle. Statistical analyses will be performed on measured variables (body mass, muscle mass, nerve fiber counts, muscle fiber cross sectional area). Results: There was no difference in muscle masses between the two groups. The tissue is currently undergoing immunohistochemical analysis. Conclusion: A brief period of intraoperative electrical stimulation does not have a myoprotective effect. The effect of electrical stimulation on the nerve will be evaluated once tissue staining has been completed.