Modality Specific Nerve Grafting

Despite given regeneration in peripheral nerves, complete functional recovery is rarely achieved. Nerve grafting is the most preferred therapy to reconstruct lost nerve segments following injury. The goal of this research project is to improve functional outcome of nerve grafting. Recent data from the Brushart Laboratory show that Schwann cells express distinct patterns of sensory and motor trophic factors that regulate axon regeneration. We hypothesize that manipulating these specific trophic factors in nerve grafts would improve axon regeneration. Based on this data, we address the two aims of this study. Aim I: Investigate the phenotype variability of Schwann cells related to different axon populations. RT-PCR will be used to analyze gene upregulation of previously identified 11 different trophic factors, followed by protein quantification. The following five groups will be investigated: Aim I-A: trophic factor gene upregulation in peripheral motor axon Schwann cells Aim I-B: trophic factor gene upregulation in dorsal root Schwann cells Aim I-C: trophic factor gene upregulation in muscle afferent axons compared to cutaneous afferent axons Aim I-C: trophic factor gene upregulation in denervated unmyelinated Schwann cells Aim II: The second part of this study will determine if reconstructing gaps in mixed nerves is more successful using cutaneous nerve or ventral root as graft. The outcome will be assayed using walking track analysis, sensory testing and retrograde labeling. Data obtained in Aim II-A will serve as a baseline which represents the current clinical practice. Mixed nerve gaps will be repaired using cutaneous nerve grafts. For Aim II-B we will investigate functional outcome of pure motor nerve grafts. Mixed nerve gaps will be repaired using pure motor nerve grafts. The outlined experiments will help clarify Schwann cell response to peripheral nerve injury. The obtained knowledge will therefore help to specifically manipulate nerve grafts. It is reasonable to assume that clinical outcome might be improved by matching nerve grafts. However, since autologous mixed nerve grafts are not available, genetically modified nerve grafts could be a possible alternative.