Direct Muscle Neurotization

Brunelli, Giorgio; Brunelli, G

doi:10.1055/s-2007-1006656

Cited by 52 publications

(69 citation statements)

References 3 publications

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“…Many previous studies 19,20,22,23,25,[28][29][30][31][32][33]36,37 did not exclude any effects from uninjured collateral nerves in denervated muscle. In the present study, the common peroneal nerve was implanted into the GM after excision of a 10-mm segment of the tibial nerve and a sensory nerve branch.…”

Section: Discussionmentioning

confidence: 98%

“…28,[30][31] However, these methods did not exclude the effect of collateral nerve input into the muscle, and thus could not determine the functional result of replacing a single nerve. In the present study, both of these issues have been addressed.…”

Section: Discussionmentioning

confidence: 99%

“…The outcome of direct nerve transplantation is dependent upon the chronicity of denervation, 23,24,28,32 regeneration distance, 24,27,30 distance between the nerve implantation site and the native motor endplate zone, 36 patient age, quantity and quality of remaining muscle mass, 28,32 status of donor nerve, and surgical technique. 25,30,33 This study is minimally biased based on these factors, because the donor nerve was transplanted immediately after transection of all branches of the recipient's nerve, and the graft was placed close to the native motor endplate zone.…”

Section: Discussionmentioning

confidence: 99%

“…In patients who lack a distal nerve segment for anastomosis, direct nerve transplantation into the denervated muscle (neurotization) [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] is indicated. This group would include those receiving a transplant of tissue-engineered muscle to repair volumetric muscle loss, because the engineered muscle does not contain host nerve tissue and thus cannot be anastomosed.…”

Section: Introductionmentioning

confidence: 99%

“…Although this method was first developed at the beginning of the 20th century, 35 its effect on muscle functionality is not fully understood. 21,22,26,28 Previous studies designed to determine whether functional recovery occurs after nerve transplantation did not investigate endpoints beyond the electrophysiological recovery. 20,22,24,27,33,34 In addition, many preclinical and clinical studies 19,22,23,25,[28][29][30][31][32][33]36,37 did not exclude the possible effects of the presence of uninjured collateral nerves on muscle function and regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Functional Recovery of Completely Denervated Muscle: Implications for Innervation of Tissue-Engineered Muscle

Kang

Olson

Atala

et al. 2012

Tissue Engineering Part A

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Tissue-engineered muscle has been proposed as a solution to repair volumetric muscle defects and to restore muscle function. To achieve functional recovery, engineered muscle tissue requires integration of the host nerve. In this study, we investigated whether denervated muscle, which is analogous to tissue-engineered muscle tissue, can be reinnervated and can recover muscle function using an in vivo model of denervation followed by neurotization. The outcomes of this investigation may provide insights on the ability of tissue-engineered muscle to integrate with the host nerve and acquire normal muscle function. Eighty Lewis rats were classified into three groups: a normal control group (n = 16); a denervated group in which sciatic innervations to the gastrocnemius muscle were disrupted (n = 32); and a transplantation group in which the denervated gastrocnemius was repaired with a common peroneal nerve graft into the muscle (n = 32). Neurofunctional behavior, including extensor postural thrust (EPT), withdrawal reflex latency (WRL), and compound muscle action potential (CMAP), as well as histological evaluations using alpha-bungarotoxin and anti-NF-200 were performed at 2, 4, 8, and 12 weeks (n = 8) after surgery. We found that EPT was improved by transplantation of the nerve grafts, but the EPT values in the transplanted animals at 12 weeks postsurgery were still significantly lower than those measured for the normal control group at 4 weeks (EPT, 155.0 -38.9 vs. 26.3 -13.8 g, p < 0.001; WRL, 2.7 -2.30 vs. 8.3 -5.5 s, p = 0.027). In addition, CMAP latency and amplitude significantly improved with time after surgery in the transplantation group ( p < 0.001, one-way analysis of variance), and at 12 weeks postsurgery, CMAP latency and amplitude were not statistically different from normal control values (latency, 0.9 -0.0 vs. 1.3 -0.7 ms, p = 0.164; amplitude, 30.2 -7.0 vs. 46.4 -26.9 mV, p = 0.184). Histologically, regeneration of neuromuscular junctions was seen in the transplantation group. This study indicates that transplanted nerve tissue is able to regenerate neuromuscular junctions within denervated muscle, and thus the muscle can recover partial function. However, the function of the denervated muscle remains in the subnormal range even at 12 weeks after direct nerve transplantation. These results suggest that tissue-engineered muscle, which is similarly denervated, could be innervated and become functional in vivo if it is properly integrated with the host nerve.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Functional Recovery of Completely Denervated Muscle: Implications for Innervation of Tissue-Engineered Muscle

Kang

Olson

Atala

et al. 2012

Tissue Engineering Part A

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Reinnervation of denervated muscle by implantation of nerve‐muscle‐endplate band graft to the native motor zone of the target muscle

Sobotka

Chen

et al. 2017

Brain and Behavior

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IntroductionMotor endplate reinnervation is critical for restoring motor function of the denervated muscle. We developed a novel surgical technique called nerve‐muscle‐endplate band grafting (NMEG) for muscle reinnervation.MethodsExperimentally denervated sternomastoid muscle in the rat was reinnervated by transferring a NMEG from the ipsilateral sternohyoid muscle to the native motor zone (NMZ) of the target muscle. A NMEG pedicle contained a block of muscle (~ 6 × 6 × 3 mm), a nerve branch with axon terminals, and a motor endplate band with numerous neuromuscular junctions. At 3 months after surgery, maximal tetanic muscle force measurement, muscle mass and myofiber morphology, motoneurons, regenerated axons, and axon‐endplate connections of the muscles were analyzed.ResultsThe mean force of the reinnervated muscles was 82% of the contralateral controls. The average weight of the treated muscles was 89% of the controls. The reinnervated muscles exhibited extensive axonal regeneration. Specifically, the mean count of the regenerated axons in the reinnervated muscles reached up to 76.8% of the controls. The majority (80%) of the denervated endplates in the target muscle regained motor innervation.ConclusionsThe NMZ of the denervated muscle is an ideal site for NMEG implantation and for the development of new microsurgical and therapeutic strategies to achieve sufficient axonal regeneration, rapid endplate reinnervation, and optimal functional recovery. NMEG‐NMZ technique may become a useful tool in the treatment of muscle paralysis caused by peripheral nerve injuries in certain clinical situations.

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Superficial or deep implantation of motor nerve after denervation: An experimental study—superficial or deep implantation of motor nerve

Aşkar

Sabuncuoğlu

2002

Microsurgery

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Neurorraphy, conventional nerve grafting technique, and artificial nerve conduits are not enough for repair in severe injuries of peripheral nerves, especially when there is separation of motor nerve from muscle tissue. In these nerve injuries, reinnervation is indicated for neurotization. The distal end of a peripheral nerve is divided into fascicles and implanted into the aneural zone of target muscle tissue. It is not known how deeply fascicles should be implanted into muscle tissue. A comparative study of superficial and deep implantation of separated motor nerve into muscle tissue is presented in the gastrocnemius muscle of rabbits. In this experimental study, 30 white New Zealand rabbits were used and divided into 3 groups of 10 rabbits each. In the first group (controls, group I), only surgical exposure of the gastrocnemius muscle and motor nerve (tibial nerve) was done without any injury to nerves. In the superficial implantation group (group II), tibial nerves were separated and divided into their own fascicles. These fascicles were implanted superficially into the lateral head of gastrocnemius muscle-aneural zone. In the deep implantation group (group III), the tibial nerves were separated and divided into their own fascicles. These fascicles were implanted around the center of the muscle mass, into the lateral head of the gastrocnemius muscle-aneural zone. Six months later, histopathological changes and functional recovery of the gastrocnemius muscle were investigated. Both experimental groups had less muscular weight than in the control group. It was found that functional recovery was achieved in both experimental groups, and was better in the superficial implantation group than the deep implantation group. EMG recordings revealed that polyphasic and late potentials were frequently seen in both experimental groups. Degeneration and regeneration of myofibrils were observed in both experimental groups. New motor end-plates were formed in a scattered manner in both experimental groups. However, they were more dense in the superficial implantation group than the deep implantation group. It was concluded that superficial implantation has a more powerful contractile capacity than that of deep implantation. We believe that this might arise from the high activity of glycolytic enzymes in peripheral muscle fibers of gastrocnemius muscle, decrease in insufficient intramuscular guidance apparatus, and intramuscular microneuroma formation at the insufficient neuromuscular junction since the motor nerve had less route to muscle fibers.

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Direct Muscle Neurotization

Cited by 52 publications

References 3 publications

Functional Recovery of Completely Denervated Muscle: Implications for Innervation of Tissue-Engineered Muscle

Functional Recovery of Completely Denervated Muscle: Implications for Innervation of Tissue-Engineered Muscle

Reinnervation of denervated muscle by implantation of nerve‐muscle‐endplate band graft to the native motor zone of the target muscle

Superficial or deep implantation of motor nerve after denervation: An experimental study—superficial or deep implantation of motor nerve

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