End‐to‐Side Neurorrhaphy Evaluation of Axonal Response and Upregulation of IGF‐I and IGF‐II in a Non‐Injury Model

This research group has introduced a model of end-to-side neurorrhaphy, in which reinnervation occurs without frank damage to donor axons. The current study used in situ hybridization to test the hypothesis that insulin-like growth factor (IGF-I and IGF-II) mRNA levels increase at the coaptation site and grafted nerve following end-to-side repair, and that this increase is associated with axonal sprouting and growth. One week after end-to-side coaptation, IGF-I mRNA was localized predominantly on the epineurial side of the graft perineurium, while IGF-II was seen mainly on the endoneurial side. IGF-I hybridization was greatest at this time and declined by 2 weeks post-procedure. No changes in IGF mRNA levels occurred in the distal donor nerve. The increase in IGF-I mRNA at 1 week preceded the appearance of myelinated axons. The presence of myelinated axons within the graft 2 weeks after end-to-side coaptation was associated with a decline in IGF-I mRNA. These data are the first to demonstrate increased IGF mRNA levels associated with axonal sprouting and growth following end-to-side neurorrhaphy. Moreover, the findings support those of earlier studies by others implicating IGFs in axonal regeneration. The increase in IGF mRNA during sprouting and axonal growth into an end-to-side coaptation indicates that the local therapeutic augmentation of endogenous IGF levels at the coaptation site may enhance axonal sprouting from a minimally injured donor nerve, and thereby increase the number of axons that reinnervate the graft.