Brief Electrical Stimulation Promotes Nerve Regeneration Following Experimental In-Continuity Nerve Injury

Shapira, Yuval; Sammons, Vanessa; Forden, Joanne; Guo, Gui Fang; Kipp, Alexander; Girgulis, Jill; Mishra, Tanmay; Alant, Jacob; Midha, Rajiv

doi:10.1093/neuros/nyy221

Cited by 33 publications

(25 citation statements)

References 44 publications

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“…ments seem rational. However, because FK506 is regarded as a potent neuroregenerative drug with serious systemic side effects,49 that ES has few differences compared with FK506 in its neuroregenerative effects has significant implications for the translational impact of ES as a therapy to augment nerve surgery because no known side effects due to ES therapy have been discussed in the literrelative muscle mass is in line with results from previous literature on ES 35,50. However, the improvement of outcome in ES groups based on walking track analysis are corroborated by the results of histological analysis.…”

supporting

confidence: 68%

“…Indeed, in nerve injury with repair animal models, ES results in a greater number of neurons regenerating their axons across the repair site in less time . This improved regenerative axonal response leads to earlier motor and sensory recovery . Furthermore, animal studies have demonstrated that ES has the capability to enhance regeneration even when nerve repair is delayed after initial injury, improving clinical utility.…”

Section: Introductionmentioning

confidence: 99%

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Comparing electrical stimulation and tacrolimus (FK506) to enhance treating nerve injuries

Pan

Halevi

et al. 2019

Muscle and Nerve

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Introduction Neuroenhancing therapies are desired because repair of nerve injuries can fail to achieve recovery. We compared two neuroenhancing therapies, electrical stimulation (ES) and systemic tacrolimus (FK506), for their capabilities to enhance regeneration in the context of a rat model. Methods Rats were randomized to four groups: ES 0.5 mA, ES 2.0 mA, FK506, and repair alone. All groups underwent tibial nerve transection and repair, and outcomes were assessed by using twice per week walking track analysis, cold allodynia response, relative muscle mass, and nerve histology. Results Electrical stimulation and FK506 groups demonstrated improved functional recovery and myelinated axon counts distal to the repair compared with repair alone. Electrical stimulation provided improvements in nerve regeneration that were not different from optimized FK506 systemic administration. Discussion Providing ES after nerve repair improved regeneration and recovery in rats, with minimal differences in therapeutic efficacy to FK506, further demonstrating its clinical potential to improve management of nerve injuries.

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supporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Comparing electrical stimulation and tacrolimus (FK506) to enhance treating nerve injuries

Pan

Halevi

et al. 2019

Muscle and Nerve

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“…Alternative complex neurosurgical procedures are possible using this model, such as multiple nerve repairs using a "stepping stone technique", nerve transfers that enables innervation of an damaged nerve from a neighboring uninjured, ultra-long segmental deficit starting at the proximal CPN to the distal DPN (> 15 cm), or electrical stimulation to enhance regeneration. [20][21][22][23][24][25][26][27] Previous studies have developed small animal models as an attempt to replicate challenging clinical scenarios, such as long gap nerve injury, in lower order species. 28-31 However, we believe that these models do not adequately replicate the neurobiological processes found in humans and other large mammals, thus highlighting a major concern in the evaluation of potential clinical products in rodent models.…”

Section: Discussionmentioning

confidence: 99%

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

Burrell

Browne

Dutton

et al. 2019

Preprint

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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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“…From a tissue engineering perspective, many novel features have been utilized for peripheral nerve regeneration [ 8 ], specifically, neurotrophic factors and anisotropic gradients, electrical stimulation [ 9 ], pluripotent stem cell derived progenitor cells [ 10 , 11 ], 3DBP [ 12 ], immuobioengineering [ 13 ], nerve differentiation strategies, simultaneous vascularization, design customization [ 14 ], and gene therapy [ 15 – 17 ]. Here we briefly reviewed to identify points of intersection between tissue engineering and machine intelligence with a particular concentration on peripheral nerve regeneration.…”

Section: Background—critical Challenges In (Re)innervationmentioning

confidence: 99%

Machine intelligence for nerve conduit design and production

et al. 2020

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Nerve guidance conduits (NGCs) have emerged from recent advances within tissue engineering as a promising alternative to autografts for peripheral nerve repair. NGCs are tubular structures with engineered biomaterials, which guide axonal regeneration from the injured proximal nerve to the distal stump. NGC design can synergistically combine multiple properties to enhance proliferation of stem and neuronal cells, improve nerve migration, attenuate inflammation and reduce scar tissue formation. The aim of most laboratories fabricating NGCs is the development of an automated process that incorporates patient-specific features and complex tissue blueprints (e.g. neurovascular conduit) that serve as the basis for more complicated muscular and skin grafts. One of the major limitations for tissue engineering is lack of guidance for generating tissue blueprints and the absence of streamlined manufacturing processes. With the rapid expansion of machine intelligence, high dimensional image analysis, and computational scaffold design, optimized tissue templates for 3D bioprinting (3DBP) are feasible. In this review, we examine the translational challenges to peripheral nerve regeneration and where machine intelligence can innovate bottlenecks in neural tissue engineering.

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Brief Electrical Stimulation Promotes Nerve Regeneration Following Experimental In-Continuity Nerve Injury

Cited by 33 publications

References 44 publications

Comparing electrical stimulation and tacrolimus (FK506) to enhance treating nerve injuries

Comparing electrical stimulation and tacrolimus (FK506) to enhance treating nerve injuries

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

Machine intelligence for nerve conduit design and production

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