Short-Term Electrical Stimulation to Promote Nerve Repair and Functional Recovery in a Rat Model

Calvey, Colleen; Zhou, Wenda; Stakleff, Kimberly Sloan; Sendelbach-Sloan, Patricia; Harkins, Amy B.; Lanzinger, William D.; Willits, Rebecca Kuntz

doi:10.1016/j.jhsa.2014.10.002

Cited by 33 publications

(43 citation statements)

References 38 publications

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“…The rapid improvement in motor function as measured by walking track analysis occurred without a corresponding increase in relative muscle mass in the ES groups compared with repair alone. This finding that ES improves functional recovery without causing a significant increase in relative muscle mass is in line with results from previous literature on ES . However, the improvement of outcome in ES groups based on walking track analysis are corroborated by the results of histological analysis.…”

Section: Discussionsupporting

confidence: 92%

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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Section: Discussionsupporting

confidence: 92%

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

Pan

Halevi

et al. 2019

Muscle and Nerve

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“…Presently, neither the frequency nor the duration of electrical stimulation have been considered in detail, although the crushed facial nerve was stimulated daily until functional recovery at 20 Hz for 30 min/day, the stimulation commencing a day after the crush injury [67,81,82]; the transected sciatic nerve was stimulated for only 20 min after delayed nerve repair [92], and for 10 min after a transection injury that was repaired via a silicone tube filled with a collagen gel [93].…”

Section: Brief Electrical Stimulation Accelerates Axon Outgrowth Acromentioning

confidence: 99%

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

2016

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Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic.

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“…22, 23 In peripheral nerve regeneration, various cell types have been utilized including skeletal muscle-derived multipotent stem cells 24 and Schwann cells. 25 Additional efforts take advantage of cell signaling to stimulate nerve growth such as nerve growth factor (NGF), 26–28 topographical cues, 29 and electrical stimulation (ES), 30–33 all of which may serve to enhance the rate of nerve regeneration. Biodegradable scaffolds derived from the materials of both natural and synthetic origin including PLA, PGA, PLGA, polycaprolactone (PCL), collagen, chitosan, and different material compositions have been used for the fabrication of nerve conduits and as well as other tissue regenerative techniques.…”

Section: Introductionmentioning

confidence: 99%

“…30–33 The benefits of ES for the regeneration of bone, cartilage, skin, spinal nerves, and peripheral nerves have been widely documented and demonstrated in the literature. 37 Electrical stimulation is a commonly used therapy to promote functional recovery of muscle and nerve tissue following injury that can result in enhanced tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

Peripheral Nerve Regeneration Strategies: Electrically Stimulating Polymer Based Nerve Growth Conduits

Anderson

Shelke

Manoukian

et al. 2015

Crit Rev Biomed Eng

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Treatment of large peripheral nerve damages ranges from the use of an autologous nerve graft to a synthetic nerve growth conduit. Biological grafts, in spite of many merits, show several limitations in terms of availability and donor site morbidity, and outcomes are suboptimal due to fascicle mismatch, scarring, and fibrosis. Tissue engineered nerve graft substitutes utilize polymeric conduits in conjunction with cues both chemical and physical, cells alone and or in combination. The chemical and physical cues delivered through polymeric conduits play an important role and drive tissue regeneration. Electrical stimulation (ES) has been applied toward the repair and regeneration of various tissues such as muscle, tendon, nerve, and articular tissue both in laboratory and clinical settings. The underlying mechanisms that regulate cellular activities such as cell adhesion, proliferation, cell migration, protein production, and tissue regeneration following ES is not fully understood. Polymeric constructs that can carry the electrical stimulation along the length of the scaffold have been developed and characterized for possible nerve regeneration applications. We discuss the use of electrically conductive polymers and associated cell interaction, biocompatibility, tissue regeneration, and recent basic research for nerve regeneration. In conclusion, a multifunctional combinatorial device comprised of biomaterial, structural, functional, cellular, and molecular aspects may be the best way forward for effective peripheral nerve regeneration.

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Short-Term Electrical Stimulation to Promote Nerve Repair and Functional Recovery in a Rat Model

Cited by 33 publications

References 38 publications

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

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

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

Peripheral Nerve Regeneration Strategies: Electrically Stimulating Polymer Based Nerve Growth Conduits

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