scholarly journals Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair

10.2196/18706 ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. e18706
Author(s):  
Maxwell Vest ◽  
Addison Guida ◽  
Cory Colombini ◽  
Kristina Cordes ◽  
Diana Pena ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerve Injury ◽  
Action Potentials ◽  
Morphological Analysis ◽  
Nerve Repair ◽  
Distal Segment ◽  
Negative Control ◽  
Functional Index ◽  
Behavioral Recovery ◽  
Sciatic Functional Index

Background 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 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. Objective 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. Methods 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 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. Results The 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. Conclusions 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 to improve outcomes after peripheral nerve injury. International Registered Report Identifier (IRRID) PRR1-10.2196/18706

scholarly journals Closing the Gap Between Mammalian and Invertebrate Peripheral Nerve Injury: Protocol for a Novel Nerve Repair (Preprint)

2020 ◽  
Author(s):  
Maxwell Vest ◽  
Addison Guida ◽  
Cory Colombini ◽  
Kristina Cordes ◽  
Diana Pena ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerve Injury ◽  
Action Potentials ◽  
Morphological Analysis ◽  
Nerve Repair ◽  
Distal Segment ◽  
Negative Control ◽  
Functional Index ◽  
Behavioral Recovery ◽  
Sciatic Functional Index

BACKGROUND 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 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. OBJECTIVE 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. METHODS 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 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. RESULTS The 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. CONCLUSIONS 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 to improve outcomes after peripheral nerve injury. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/18706

scholarly journals Comparative Behavioral Assessment of Lewis and Nude Rats after Peripheral Nerve Injury

2020 ◽  
Vol 70 (3) ◽  
pp. 233-238
Author(s):  
Ebrahim Alawadhi ◽  
Tak- Ho Chu ◽  
Rajiv Midha
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Behavioral Assessment ◽  
Sensory Function ◽  
Suitable Model ◽  
Functional Index ◽  
Slip Ratio ◽  
Nude Rats ◽  
Sciatic Functional Index

Cell therapy has shown potential in the field of peripheral nerve repair, and research using rodents is a critical and essential step toward clinical development of this approach. Traditionally, most experimental peripheral nerve injuries are conducted in inbred Lewis or outbred Sprague–Dawley strains. However, transplantation of xenogeneic cells such as human-derived cells typically triggers rejection in these animals. An alternative approach is to use immunodeficient animals, such as athymic nude rats. The lack of functional T cells in these animals renders them more accommodating to foreign cells from a different host. Currently, no literature exists regarding sensorimotor behavioral assessment of nude rats after peripheral nerve injury. To this end, we compared the functional recovery during a 6-wk period of behavioral testing of Lewis and nude rats after unilateral sciatic nerve crushing injury. Three sensorimotor behavioral assessments were performed weekly: a ladder rungwalking task to assess slip ratio and cross duration, von Frey nociception testing to determine the paw withdrawal threshold thus monitoring the regaining of sensory function, and sciatic functional index evaluation to monitor the recovery of integrated motor function. Both strains demonstrated significant sensory and motor deficits in the first week after injury, with a slight regain of sensory function, reduced slip ratio, and increased sciatic functional index starting at 2 wk. No significance difference existed between nude and Lewis rats in their recovery courses. We conclude that nude rats are a suitable model for behavioral training and assessment for cell transplantation studies in peripheral nerve injury and repair.

scholarly journals Correlation between parameters of electrophysiological, histomorphometric and sciatic functional index evaluations after rat sciatic nerve repair

2006 ◽  
Vol 64 (3b) ◽  
pp. 750-756 ◽  
Author(s):  
Roberto Sergio Martins ◽  
Mario Gilberto Siqueira ◽  
Ciro Ferreira da Silva ◽  
José Píndaro Pereira Plese
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Fiber Diameter ◽  
Nerve Repair ◽  
Neural Regeneration ◽  
Poor Correlation ◽  
Functional Index ◽  
Rat Sciatic Nerve ◽  
Sciatic Functional Index

The rat sciatic nerve is a well-established model for the study of recovery from peripheral nerve injuries. Traditional methods of assessing nerve regeneration after nerve injury and repair, such as electrophysiology and histomorphometry, despite widely used in neural regeneration experiments, do not necessarily correlate with return of motor and sensory functions. The aim of this experimental study is to investigate the possible correlation between several parameters of peripheral nerve regeneration after repair of sectioned sciatic nerve in Wistar rat. A two-stage approach was used to obtain 17 parameters after electrophysiological, morphometric and sciatic functional index evaluations. Pearson's correlation analysis was performed between these results. Only two positives correlations between different classes of peripheral nerve assessments were noted, between sciatic functional index and proximal nerve fiber diameter (r=0.56, p<0.01) and between sciatic functional index and distal fiber diameter (r=0.50, p<0.01). The data presented in our study demonstrates that there is a poor correlation between the sciatic functional index and outcome measures of electrophysiological and morphometric evaluations.

scholarly journals A study on graphene composites for peripheral nerve injury repair under electrical stimulation

RSC Advances ◽  
2019 ◽  
Vol 9 (49) ◽  
pp. 28627-28635 ◽  
Author(s):  
Zhiqiang Huang ◽  
Zhenzhao Guo ◽  
Manman Sun ◽  
Shaomao Fang ◽  
Hong Li
Keyword(s):  
Electrical Stimulation ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Nerve Repair ◽  
Effective Alternative ◽  
Peripheral Nerve Repair ◽  
Injury Repair

Electrical stimulation (ES) provides an effective alternative to peripheral nerve repair via conductive scaffolds.

FLEXOR TENDON AND PERIPHERAL NERVE REPAIR

Hand Surgery ◽  
2002 ◽  
Vol 07 (01) ◽  
pp. 83-100 ◽  
Author(s):  
Judith A. Bell Krotoski
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Flexor Tendon ◽  
Nerve Repair ◽  
Hand Function ◽  
Tendon Injury ◽  
Finger Movement ◽  
Flexor Tendon Injury ◽  
Direct Injury

Any restoration of hand function following tendon and nerve injury has to include the repair or replacement of the hand's ability to perform a great many tasks. It is hard at first to appreciate fully the loss that occurs with flexor tendon injury. With loss of flexor tendons operating at the fingers or thumb, they cannot be fully closed and the hand is impaired for grasp and release as it interfaces with objects. But, sensibility can also be compromised from tendon injury even without direct injury to nerve, as object recognition in the absence of vision requires finger movement. When peripheral nerve injury is combined with flexor tendon injury, sensibility is directly impaired. There is a loss in the sense of finger or thumb position, pain, temperature, and touch/pressure recognition, in addition to the tendon injury.

Effect of ropivacaine injected into peripheral nerve in rats using the sciatic functional index

2000 ◽  
Vol 17 (Supplement 19) ◽  
pp. 115
Author(s):  
H. Bouaziz ◽  
G. B. Lan ◽  
Y. Grignon ◽  
A. L. Leblanc ◽  
M. Merle ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Functional Index ◽  
Sciatic Functional Index

scholarly journals Debates to personal conclusion in peripheral nerve injury and reconstruction: A 30-year experience at Chang Gung Memorial Hospital

2016 ◽  
Vol 49 (02) ◽  
pp. 144-150 ◽  
Author(s):  
David Chwei-Chin Chuang
Keyword(s):  
Peripheral Nerve ◽  
Brachial Plexus ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Nerve Repair ◽  
Memorial Hospital ◽  
Chang Gung Memorial Hospital ◽  
The Past ◽  
Nerve Transfers ◽  
Facial Synkinesis

ABSTRACTSignificant progress has been achieved in the science and management of peripheral nerve injuries over the past 40 years. Yet there are many questions and few answers. The author, with 30 years of experience in treating them at the Chang Gung Memorial Hospital, addresses debates on various issues with personal conclusions. These include: (1) Degree of peripheral nerve injury, (2) Timing of nerve repair, (3)Technique of nerve repair, (4) Level of brachial plexus injury,(5) Level of radialnerve injury,(6) Traction avulsion amputation of major limb, (7) Proximal Vs distal nerve transfers in brachial plexus injuries and (8) Post paralysis facial synkinesis.

Dose and duration of nerve growth factor (NGF) administration determine the extent of behavioral recovery following peripheral nerve injury in the rat

2011 ◽  
Vol 229 (2) ◽  
pp. 460-470 ◽  
Author(s):  
Stephen W.P. Kemp ◽  
Aubrey A. Webb ◽  
Sundeep Dhaliwal ◽  
Shahbaz Syed ◽  
Sarah K. Walsh ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Behavioral Recovery ◽  
Nerve Growth

scholarly journals A Porcine Model of Peripheral Nerve Injury Enabling Ultra-Long Regenerative Distances: Surgical Approach, Recovery Kinetics, and Clinical Relevance

2019 ◽  
Author(s):  
Justin C. Burrell ◽  
Kevin D. Browne ◽  
John L. Dutton ◽  
Suradip Das ◽  
Daniel P. Brown ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Surgical Approach ◽  
Peripheral Nerve Injury ◽  
Peroneal Nerve ◽  
Porcine Model ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Common Peroneal Nerve ◽  
Nerve Autograft

AbstractApproximately 20 million Americans currently experience residual deficits from traumatic peripheral nerve injury. Despite recent advancements in surgical technique, peripheral nerve repair typically results in poor functional outcomes due to prolonged periods of denervation resulting from long regenerative distances coupled with relatively slow rates of axonal regeneration. Development of novel surgical solutions requires valid preclinical models that adequately replicate the key challenges of clinical peripheral nerve injury. Our team has developed a porcine model using Yucatan minipigs that provides an opportunity to investigate peripheral nerve regeneration using different nerves tailored for a specific mechanism of interest, such as (1) nerve modality: motor, sensory, and mixed-modality; (2) injury length: short versus long gap; and (3) total regenerative distance: proximal versus distal injury. Here, we describe a comprehensive porcine model of two challenging clinically relevant procedures for repair of long segmental lesions (≥ 5 cm) – the deep peroneal nerve repaired using a sural nerve autograft and the common peroneal nerve repaired using a saphenous nerve autograft – each featuring ultra-long total regenerative distances (up to 20 cm and 27 cm, respectively) to reach distal targets. This paper includes a detailed characterization of the relevant anatomy, surgical approach/technique, functional/electrophysiological outcomes, and nerve morphometry for baseline and autograft repaired nerves. These porcine models of major peripheral nerve injury are suitable as preclinical, translatable models for evaluating the efficacy, safety, and tolerability of next-generation artificial nerve grafts prior to clinical deployment.

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