Journal of Plastic, Reconstructive & Aesthetic Surgery
Effects of repeated transection and coaptation of peripheral nerves on axonal regeneration and motoneuron survival
Introduction
Technical options for reanimation of a paralyzed face include nerve transfer and free muscle transplantation.1, 2, 3–4 For recent cases of facial nerve injury, it is assumed that the facial musculature on the affected side remains viable and is able to be reinnervated.5 Therefore, nerve repair with cross-facial nerve grafts or masseter nerve transfer is preferred.6, 7–8 For longstanding cases of facial palsy, it is not possible for the paralyzed mimetic muscle to regain function. Thus, microneurovascular muscle transplantation should be chosen to reinstitute major facial movement. However, both techniques carry a risk of failure, as unknown myopathy can sometimes occur. In the authors’ own practice, there existed special cases in which the preoperative examination of the donor nerve function revealed no functional impairment, denervation time of the paralyzed face was less than a year, or MRI scanning suggested no tumor invasion of the trigeminal nucleus (in case of masseter nerve transfer), but the re-innervated musculature or the muscle transplant failed to generate sufficient excursion 6–12 months postoperatively. Under such circumstance, salvage procedure with muscle transfer is under consideration.9, 10 Nevertheless, it could be struggling for the surgeons and patients to decide whether to reuse the original donor nerve or to seek for another substitute to power the new muscle, as employment of a second nerve would inevitably result in additional donor site morbidity. Reuse of the primary donor nerve may be an option in this situation, but it has not been well studied thus far whether re-coaptation of the previously used nerve is as likely to gain successful outcome as the primary attempt.
One key question for reusing the primary donor nerve is whether the quality of the salvaged nerve is comparable to that of a fresh one. After transection and surgical coaptation, axons have the capacity to regenerate at a rate of approximately 1 mm per day,11 but axonal loss can occur while the nerve is regenerating at the coaptation interface due to tributary outgrowth.12, 13 Furthermore, it has been reported that peripheral nerve injury can elicit apoptosis of motoneurons depending on injury type and the distance from the lesion site to the cell body,14, 15 undermining functional recovery. Despite these findings, there have been few investigations regarding the effect of repeated nerve injury on axonal regeneration and motoneuron survival. Some publications reported accelerated axonal growth induced by a lesion 7–14 days prior,16, 17 but recent studies have indicated loss of motoneuron and impairment of functional recovery caused by repeated crush injury.18, 19, 20 However, to the best of our knowledge, there has been no study reporting the impact of repeated nerve transection and coaptation with longer intervals on nerve regeneration and motoneuron survival.
The present study simulated the surgical procedure by repeatedly transecting and suturing the sciatic nerve in rats at intervals of 8 weeks. We investigated axonal regeneration, muscle recovery, and motoneuron survival after one-time and repeated nerve injury and repair. The results will be helpful for the understanding of nerve regeneration after repeated injury with reasonable expectations in salvage procedures.
Section snippets
Animals
Twenty-four male Sprague Dawley rats (200–220 g) were used for animal modeling. The animals were housed under specific pathogen-free conditions with the approval of the Institutional Animal Care and Use Committee of Shanghai Ninth People's Hospital. All procedures were performed aseptically, with animals deeply anesthetized using intraperitoneal injection of pentobarbital (40 mg/kg).
Transection and coaptation of the sciatic nerve
The animals were randomly divided into two groups: (1) one-time transection and coaptation of the sciatic nerve
Effect of repeated nerve transection and coaptation on muscle recovery
Peripheral nerve injury results in denervation atrophy of its innervated muscle that recovers as nerves regenerate and re-innervate.22 In the present study, one-time transection and coaptation of the sciatic nerve elicited a significant decrease in the ipsilateral gastrocnemius muscle weight compared to the contralateral counterpart 8 weeks postinjury (1.576 ± 0.2713 g versus 2.956 ± 0.6878 g, p = 0.0006). Reasonably, repeated nerve transection and repair led to a significantly lower wet weight
Discussion
Salvage procedure with free muscle transplantation can sometimes be necessary for facial reanimation in scenarios where the previous nerve repair fails to work.23 It is often speculated that using a new donor nerve other than the old one is beneficial for better outcomes, but additional risk and loss of donor function should be taken into consideration. Repeated utilization of the same donor nerve is still possible, yet there is a lack of evidence regarding whether the quality of a repeatedly
Acknowledgments
This study was supported by grants from the Shanghai Municipal Commission of Health and Family Planning Program to Dr. Wei Wang, Project number: 201504253, and from the Special Fund for Science and Technology Innovation of Shanghai Jiao Tong University to Dr. Wei Wang, Project number: YG2016MS10.
Conflict of interest
None of the authors has financial interests in any of the products, devices, or drugs mentioned in this manuscript.
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