Abstract
BackgroundOutcomes after peripheral nerve injuries are poor despite current nerve repair techniques. Currently, there is no conclusive evidence that mammalian axons are capable of spontaneous fusion after transection. Notably, certain invertebrate species are able to auto-fuse after transection. Although mammalian axonal auto-fusion has not been observed experimentally, no mammalian study to date has demonstrated regenerating axolemmal membranes contacting intact distal segment axolemmal membranes to determine whether mammalian peripheral nerve axons have the intrinsic mechanisms necessary to auto-fuse after transection.ObjectiveThis study aims to assess fusion competence between regenerating axons and intact distal segment axons by enhancing axon regeneration, delaying Wallerian degeneration, limiting the immune response, and preventing myelin obstruction.MethodsThis study will use a rat sciatic nerve model to evaluate the effects of a novel peripheral nerve repair protocol on behavioral, electrophysiologic, and morphologic parameters. This protocol consists of a variety of preoperative, intraoperative, and postoperative interventions. Fusion will be assessed with electrophysiological conduction of action potentials across the repaired transection site. Axon-axon contact will be assessed with transmission electron microscopy. Behavioral recovery will be analyzed with the sciatic functional index. A total of 36 rats will be used for this study. The experimental group will use 24 rats and the negative control group will use 12 rats. For both the experimental and negative control groups, there will be both a behavior group and another group that will undergo electrophysiological and morphological analysis. The primary end point will be the presence or absence of action potentials across the lesion site. Secondary end points will include behavioral recovery with the sciatic functional index and morphological analysis of axon-axon contact between regenerating axons and intact distal segment axons.ResultsThe author is in the process of grant funding and institutional review board approval as of March 2020. The final follow-up will be completed by December 2021.ConclusionsIn this study, the efficacy of the proposed novel peripheral nerve repair protocol will be evaluated using behavioral and electrophysiologic parameters. The author believes this study will provide information regarding whether spontaneous axon fusion is possible in mammals under the proper conditions. This information could potentially be translated to clinical trials if successful to improve outcomes after peripheral nerve injury.International Registered Report Identifier (IRRID)PRR1-10.2196/18706
Highlights
BackgroundPeripheral nerve injuries (PNIs) are devastating and life-altering events that affect 20 million Americans per year and result in an annual economic cost of $150 billion [1]
The author believes this study will provide information regarding whether spontaneous axon fusion is possible in mammals under the proper conditions. This information could potentially be translated to clinical trials if successful to improve outcomes after peripheral nerve injury
Auto-fusion occurs with high specificity, as existing evidence suggests that regenerating axons can recognize and fuse with their original distal ends
Summary
BackgroundPeripheral nerve injuries (PNIs) are devastating and life-altering events that affect 20 million Americans per year and result in an annual economic cost of $150 billion [1]. After primary repair of a peripheral nerve laceration, regenerating axons frequently contact distal nerve segments that have undergone Wallerian degeneration (WD). Auto-fusion occurs with high specificity, as existing evidence suggests that regenerating axons can recognize and fuse with their original distal ends. The mechanisms underlying this specificity are still being investigated, but it is believed that there is overlap with the molecular players involved in auto-fusion. Mammalian axonal auto-fusion has not been observed experimentally, no mammalian study to date has demonstrated regenerating axolemmal membranes contacting intact distal segment axolemmal membranes to determine whether mammalian peripheral nerve axons have the intrinsic mechanisms necessary to auto-fuse after transection
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