Use of Electrical Stimulation at Different Current Levels to Promote Recovery After Peripheral Nerve Injury in Rats

Lu, Ming; Tsai, Chin Chuan; Chen, Shih Che; Tsai, Fuu Jen; Yao, Chun Hsu; Chen, Yueh Sheng

doi:10.1097/ta.0b013e318182351a

Cited by 39 publications

(22 citation statements)

References 21 publications

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“…Furthermore, a nonconductive nerve scaffold will isolate the electrical signals from surrounding tissues, such as muscle or other nerve tissue. Comparing previous studies using percutaneous electrical stimulation which stimulates a large surrounding area and superficial overlying muscles without accurate location of deep targets [54,55], our method provides a more precise effect on the transplanted stem cell.…”

Section: Discussionmentioning

confidence: 88%

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

et al. 2018

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Peripheral nerve injuries often lead to incomplete recovery and contribute to significant disability to approximately 360,000 people in the USA each year. Stem cell therapy holds significant promise for peripheral nerve regeneration, but maintenance of stem cell viability and differentiation potential in vivo are still major obstacles for translation. Using a made-in-house 96-well vertical electrical stimulation (ES) platform, we investigated the effects of different stimulating pulse frequency, duration and field direction on human neural crest stem cell (NCSC) differentiation. We observed dendritic morphology with enhanced neuronal differentiation for NCSCs cultured on cathodes subject to 20 Hz, 100μs pulse at a potential gradient of 200 mV/mm. We further evaluated the effect of a novel cell-based therapy featuring optimized pulsatile ES of NCSCs for in vivo transplantation following peripheral nerve regeneration. 15 mm critical-sized sciatic nerve injuries were generated with subsequent surgical repair in sixty athymic nude rats. Injured animals were randomly assigned into five groups (N = 12 per group): blank control, ES, NCSC, NCSC + ES, and autologous nerve graft. Optimized ES was applied immediately after surgical repair for 1 h in ES and NCSC + ES groups. Recovery was assessed by behavioral (CatWalk gait analysis), wet muscle-mass, histomorphometric, and immunohistochemical analyses at either 6 or 12 weeks after surgery (N = 6 per group). Gastrocnemius muscle wet mass measurements in ES + NCSC group were comparable to autologous nerve transplantation and significantly higher than other groups (p < 0.05). Quantitative histomorphometric analysis and catwalk gait analysis showed similar improvements by ES on NCSCs (p < 0.05). A higher number of viable NCSCs was shown via immunochemical analysis, with higher Schwann cell (SC) differentiation in the NCSC + ES group compared to the NCSC group (p < 0.05). Overall, ES on NCSC transplantation significantly enhanced nerve regeneration after injury and repair, and was comparable to autograft treatment. Thus, ES can be a potent alternative to biochemical and physical cues for modulating stem cell survival and differentiation. This novel cell-based intervention presents an effective and safe approach for improved outcomes after peripheral nerve repair.

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Section: Discussionmentioning

confidence: 88%

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

et al. 2018

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“…21 It was concluded that increasing the intensity of the electrical signal led to decreased function of the regenerated nerve. 96 Previous studies reported that the immediate application of ES following injury led to better nerve regeneration. 97 The intensity of applied ES, frequency, duration, and timing following nerve injury plays an important role in determining tissue healing.…”

Section: Effect Of Electrical Stimulation On Neuronsmentioning

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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“…It has also been explored that placing direct current at the cathode would form adhesion-associated proteoglycan to accelerate nerve regeneration [22]. In our previous researches in which we studied injured nerves related to the hindlimbs, we recognized that acupuncture and electroacupuncture could accelerate the maturity of regenerated nerves with larger mean values of axon number, endoneurial area, blood vessel number, and blood vessel area as compared with the controls [13, 23]. This was similar to our current study of the injured median nerve related to the forelimbs.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture and Acupuncture Promote the Rat’s Transected Median Nerve Regeneration

Yao

Chen

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Background. Acupuncture and electroacupuncture treatments of damaged nerves may aid nerve regeneration related to hindlimb function, but the effects on the forelimb-related median nerve were not known. Methods. A gap was made in the median nerve of each rat by suturing the stumps into silicone rubber tubes. The influences of acupuncture and electroacupuncture treatments on transected median nerve regeneration were evaluated from morphological, electrophysiological, and functional angles. Results. Morphologically, the group receiving acupuncture and electroacupuncture treatments had larger total nerve area and blood vessel number compared with the controls. Electrophysiologically, the group receiving electroacupuncture had significantly larger amplitude and larger area of the evoked muscle action potentials compared with the controls. Functionally, the acupuncture and electroacupuncture treatments enhanced the injured paw's ability to regain its grasping power and resulted in a faster efficiency to a new bilateral balance. Conclusion. Our findings provide multiapproach evidence of the efficacy of acupuncture and electroacupuncture treatments to the regeneration of median nerve. Indeed, acupuncture and electroacupuncture appear to have positive effects on the regeneration processes. This platform is beneficial to further study the clinical application of acupuncture and electroacupuncture alternative treatments on nerve-injured patients.

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Use of Electrical Stimulation at Different Current Levels to Promote Recovery After Peripheral Nerve Injury in Rats

Cited by 39 publications

References 21 publications

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

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

Electroacupuncture and Acupuncture Promote the Rat’s Transected Median Nerve Regeneration

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