Currently submitted to: JMIR Research Protocols
Date Submitted: Mar 13, 2020
Open Peer Review Period: Mar 12, 2020 - May 7, 2020
(currently open for review)
Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: A Novel Nerve Repair Protocol
Outcomes 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 have the ability 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.
This 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.
This 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 pre-, intra-, and post- operative 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 a behavior group and another group that will undergo electrophysiological and morphological analysis. The primary endpoint will be the presence or absence of action potentials across the lesion site. Secondary endpoints will include behavioral recovery with the sciatic functional index and morphological analysis of axon-axon contact between regenerating axons and intact distal segment axons.
We are in the process of grant funding and IRB approval as of March 2020. The final follow-up will be completed by December 2021.
In 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 in an effort to improve outcomes after peripheral nerve injury.
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