Axonal Regeneration Through Autologous Grafts: Does the Axonal Load of the Graft Influence Successful Outcomes?
Miranda Chacon, BS1, Jeff W. Lichtman, MD PhD2, Adriaan O. Grobbelaar, MD3, Howard Langstein, MD1, Jonathan I. Leckenby, MD MRCS1.
1University of Rochester, Rochester, NY, USA, 2Harvard University, Cambridge, MA, USA, 3The Royal Free NHS Foundation Trust, London, United Kingdom.
Early work has demonstrated that not every axon successfully regenerates across a neurorrhaphy, and that higher axon counts correlate with improved outcomes in facial reanimation surgeries. The purpose of this study was to investigate the impact of varying axonal counts in autologous grafts on the functional outcome of nerve repair surgery.
Six week old YFP-16 female rats were allocated into three groups: Direct Nerve Repair (DNR, n=50), Small Nerve Graft (common peroneal nerve, SNG, n=50), and Large Nerve Graft (sciatic nerve, LNG, n=50). All grafts were inset into the Posterior Auricular Nerve. Ear movement recovery was monitored as a measure of functional outcome in the affected ear, with the unaffected ear used as a control. At various post-operative weeks (POW), excised specimens were imaged with electron microscopy. Axon counts were measured proximal (PAC) and distal (DAC) to the neurorrhaphy as well as within the graft. Total Success Ratio [TSR=(DAC/PAC)], the ratio of axons to successfully regenerate across the specimen, was calculated.
The posterior auricular nerve (PAN), sciatic nerve (ScN), and common peroneal nerve (CPN) had varying axon counts, with a significant differences between ScN and CPN. PAN demonstrated the lowest counts. For the DNR group, the distal count was significantly lower than the proximal at all POWs, with a maximum TSR of 80%. LNG had a significantly larger distal axon count than SNG at POW12 and beyond. The TSR for SNG and LNG were significantly lower at all POWs when compared to DNR, with maximums of 38% and 56% respectively. All groups reached maximum TSR at POW12. A significant direct relationship was present between distal axon counts and ear motion recovery.
These results demonstrate a significant correlation between counts distal to neurorrhaphy in autologous grafts and motion recovery, supporting the conclusion that axon counts in autologous grafts influence the functional outcome of surgical repair. Nerve grafts with a greater native axonal count were demonstrated to yield superior nerve regeneration results.
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