Future Perspectives in the Management of Nerve Injuries

Mackinnon, Susan E.

doi:10.1055/s-0038-1639353

Cited by 29 publications

(24 citation statements)

References 18 publications

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“…All data are mean ± SD, n = 9 per group [Color figure can be viewed at wileyonlinelibrary.com]4 | DISCUSSIONOur hypothesis that supplementing nerve repair with either ES or FK506 would improve regeneration and recovery compared with repair alone was not rejected. This finding was not intuitive because the mechanisms by which these neuroenhancing therapies promote their effects are slightly different 44,45. FK506 can bind immunophilin receptors contained on neurons, leading to activation of heat-shock proteins and, in turn, increased expression of growth-associated genes, such as growth-associated protein (GAP)-43, and activation of the mitogen-activated protein kinase (originally called extracellular signal-regulated kinase) pathway 14,[46][47][48].…”

mentioning

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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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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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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“…While each has shown some promise in treating patients, none has provided a single universally applicable cure for the consequences of TPNI and they are also not without significant pitfalls or potent side effect profiles. Surgical interventions have been extensively reviewed by several authors (Campbell, ; Dvali & Mackinnon, ; Mackinnon, ; Siemionow & Brzezicki, ); this section will highlight the usefulness of novel non‐surgical therapeutic approaches in promoting myelination following peripheral neurotrauma (Table ).…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Peripheral nerve injury and myelination: Potential therapeutic strategies

Modrak

Talukder

Gurgenashvili

et al. 2019

J of Neuroscience Research

138

118

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Traumatic peripheral nerve injury represents a major clinical and public health problem that often leads to significant functional impairment and permanent disability. Despite modern diagnostic procedures and advanced microsurgical techniques, functional recovery after peripheral nerve repair is often unsatisfactory. Therefore, there is an unmet need for new therapeutic or adjunctive strategies to promote the functional recovery in nerve injury patients. In contrast to the central nervous system, Schwann cells in the peripheral nervous system play a pivotal role in several aspects of nerve repair such as degeneration, remyelination, and axonal growth. Several non‐surgical approaches, including pharmacological, electrical, cell‐based, and laser therapies, have been employed to promote myelination and enhance functional recovery after peripheral nerve injury. This review will succinctly discuss the potential therapeutic strategies in the context of myelination following peripheral neurotrauma.

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“…Calibrated von Frey monofilaments (1.4-15 g) were used to evaluate sensory reinnervation to the plantar footpad. 9 Three consecutive paw withdrawals to an individual monofilament constituted a positive response.…”

Section: Analysesmentioning

confidence: 99%

“…To inform future clinical trials, the goal of this study was to compare the lengths of axon extension and sensorimotor behavioral outcomes of CES and PES in an animal model of nerve autograft which is the most commonly used method to repair a nerve gap. 8,9 Nerve grafts are commonly used following oncological resection, brachial plexus repair, facial reanimation, and chronic injury repair. 10 Since these surgeries are elective, it is feasible to condition one week prior.…”

Section: Introductionmentioning

confidence: 99%

Conditioning Electrical Stimulation Is Superior to Postoperative Electrical Stimulation in Enhanced Regeneration and Functional Recovery Following Nerve Graft Repair

Senger

Chan

et al. 2020

Neurorehabil Neural Repair

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Background. Autologous nerve graft is the most common clinical intervention for repairing a nerve gap. However, its regenerative capacity is decreased in part because, unlike a primary repair, the regenerating axons must traverse 2 repair sites. Means to promote nerve regeneration across a graft are needed. Postoperative electrical stimulation (PES) improves nerve growth by reducing staggered regeneration at the coaptation site whereas conditioning electrical stimulation (CES) accelerates axon extension. In this study, we directly compared these electrical stimulation paradigms in a model of nerve autograft repair. Methods. To lay the foundation for clinical translation, regeneration and reinnervation outcomes of CES and PES in a 5-mm nerve autograft model were compared. Sprague-Dawley rats were divided into: ( a) CES, ( b) PES, and ( c) no stimulation cohorts. CES was delivered 1 week prior to nerve cut/coaptation, and PES was delivered immediately following coaptation. Length of nerve regeneration (n = 6/cohort), and behavioral testing (n = 16/cohort) were performed at 14 days and 6 to 14 weeks post-coaptation, respectively. Results. CES treated axons extended 5.9 ± 0.2 mm, significantly longer than PES (3.8 ± 0.2 mm), or no stimulation (2.5 ± 0.2 mm) ( P < .01). Compared with PES animals, the CES animals had significantly improved sensory recovery (von Frey filament testing, intraepidermal nerve fiber reinnervation) ( P < .001) and motor reinnervation (horizontal ladder, gait analysis, nerve conduction studies, neuromuscular junction analysis) ( P < .01). Conclusion. CES resulted in faster regeneration through the nerve graft and improved sensorimotor recovery compared to all other cohorts. It is a promising treatment to improve outcomes in patients undergoing nerve autograft repair.

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Future Perspectives in the Management of Nerve Injuries

Abstract: Taken together this evidence suggests that nerve transfers do offer an alternative technique along with tendon transfers, nerve repair, and nerve grafts.

Cited by 29 publications

References 18 publications

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

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

Peripheral nerve injury and myelination: Potential therapeutic strategies

Conditioning Electrical Stimulation Is Superior to Postoperative Electrical Stimulation in Enhanced Regeneration and Functional Recovery Following Nerve Graft Repair

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