Immunohistologic analysis of spontaneous recurrent laryngeal nerve reinnervation in a rat model

Rosko, Andrew J.; Kupfer, Robbi A.; Oh, Sang Su; Haring, Catherine T.; Feldman, Eva L.; Hogikyan, Norman D.

doi:10.1002/lary.27004

Cited by 13 publications

(12 citation statements)

References 38 publications

(45 reference statements)

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“…Iatrogenic recurrent laryngeal nerve (RLN) injury is a common complication of anterior neck surgical procedures, such as cervical spinal surgery or thyroidectomy . Injury to the RLN results in ipsilateral vocal fold (VF) paralysis that may contribute to dysphagia, dysphonia, and/or dyspnea (i.e., swallow, voice, and respiratory dysfunction, respectively) . These conditions are devastating for patients, especially if chronically persistent, as they are associated with poor quality of life, major depression, increased financial burden, and decreased general health .…”

Section: Introductionmentioning

confidence: 99%

“…These conditions are devastating for patients, especially if chronically persistent, as they are associated with poor quality of life, major depression, increased financial burden, and decreased general health . Furthermore, effective treatment options to promote RLN regeneration and restore full functionality of the injured VF are lacking …”

Section: Introductionmentioning

confidence: 99%

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Automated Quantification of Vocal Fold Motion in a Recurrent Laryngeal Nerve Injury Mouse Model

et al. 2018

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Objectives/Hypothesis: The goal of this study was to objectively examine vocal fold (VF) motion dynamics after iatrogenic recurrent laryngeal nerve (RLN) injury in a mouse surgical model. Furthermore, we sought to identify a method of inducing injury with a consistent recovery pattern from which we can begin to evaluate spontaneous recovery and test therapeutic interventions.Study Design: Animal model. Methods: The right RLN in C57BL/6J mice was crushed for 30 seconds using an aneurysm clip with 1.3-N closing force. Transoral laryngoscopy enabled visualization of VF movement prior to surgery, immediately post-crush, and at two endpoints: 3 days (n = 5) and 2 weeks (n = 5). VF motion was quantified with our custom motion-analysis software. At each endpoint, RLN samples were collected for transmission electron microscopy for correlation with VF motion dynamics.Results: Our VF tracking software permitted automated quantification of several measures of VF dynamics, such as range and frequency of motion. By 2 weeks post-injury, the frequency of VF movement on the right (injured) side equaled the left, yet range of motion only partially recovered. These objective outcome measures enabled detection of VF dysfunction that persisted at 2 weeks post-crush. Transmission electron microscopy images revealed RLN degeneration 3 days post-crush and partial regeneration at 2 weeks, consistent with functional results obtained with automated VF tracking.Conclusions: Our motion-analysis software provides novel objective, quantitative, and repeatable metrics to detect and describe subtle VF dysfunction in mice that corresponds with underlying RLN degeneration and recovery. Adaptation of our tracking software for use with human patients is underway.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Automated Quantification of Vocal Fold Motion in a Recurrent Laryngeal Nerve Injury Mouse Model

et al. 2018

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“…Unilateral injured RLN shows a robust capacity for regeneration; axons sprout from the proximal stump to seek open endoneurial tubules as new pathways through which to reach the laryngeal musculature as early as 1 week after injury. 20 Our previous study showed that spontaneous RLN regeneration is involved in reinnervation of the laryngeal muscles following laryngeal denervation. 21 Functional recovery of the affected vocal fold depends on reinnervation and synkinesis.…”

Section: Discussionmentioning

confidence: 99%

Main branch of ACN‐to‐RLN for management of laryngospasm due to unilateral vocal cord paralysis

et al. 2019

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Objectives/Hypothesis This study explored the feasibility and efficiency of main branch of ansa cervicalis nerve (ACN)‐to‐recurrent laryngeal nerve (RLN) anastomosis for management of paroxysmal laryngospasm due to unilateral vocal cord paralysis (UVCP). Methods Thirteen patients who underwent main branch of ACN‐to‐RLN anastomosis for management of paroxysmal laryngospasm due to UVCP were enrolled in the present study. Multidimensional assessments, including videostroboscopy, voice assessment, and laryngeal electromyography (LEMG), were performed preoperatively and postoperatively. Results This series was limited to UVCP with iatrogenic causes, including thyroidectomy, cervical spine surgery, and thoracic surgery. After main branch of ACN‐to‐RLN anastomosis, all cases showed significant airway improvement, and laryngospasm was completely abolished in 92.3% (12 of 13) of cases. Videostroboscopy showed that the bulging and paradoxical adduction of the affected vocal cord during a sniff were abolished immediately after operation, and there was no significant difference in vocal fold position or glottal closure before versus after the operation. LEMG showed that the postoperative recruitment and amplitude of voluntary motor unit potential in the affected thyroarytenoid muscle during a sniff were significantly decreased compared to preoperative values, and postoperative recruitment showed significant improvement during phonation compared to that preoperatively. Voice assessment showed that there were no significant differences in overall grade, roughness, breathiness, jitter (local), shimmer (local), noise‐to‐harmonics ratio, or maximum phonation time after the operation compared to the preoperative values. Conclusions Main branch of ACN‐to‐RLN anastomosis could have long‐lasting efficacy in the management of paroxysmal laryngospasm due to UVCP, with no apparent compromise of voice quality. Level of Evidence 4 Laryngoscope, 130:2412–2419, 2020

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“…Cross‐sections of 14 μm were obtained. Muscle sections were processed with acetylcholinesterase (motor endplates), α‐bungarotoxin (acetylcholine receptors), and a neurofilament antibody (nerve fibers) as described in our previously published protocol 14 . Images were taken at 40× magnification using a Nikon A1 confocal microscope (Nikon, Tokyo, Japan); the microscopic images were converted to digital images for analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Cross-sections of 14 μm were obtained, and the sections were stained with a neurofilament antibody as previously described. 14 Fluorescent microscopy at 20× magnification was performed via a Nikon Microphot FXA fluorescent microscope (Nikon). The microscopic images were converted to digital images for quantification.…”

Section: Nerve Histomorphometric Analysismentioning

confidence: 99%

Delivery of Interleukin‐4–Encoding Lentivirus Using Multiple‐Channel Bridges Enhances Nerve Regeneration

et al. 2020

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Objectives/Hypothesis: Facial nerve injury is a source of major morbidity. This study investigated the neuroregenerative effects of inducing an anti-inflammatory environment when reconstructing a facial nerve defect with a multichannel bridge containing interleukin-4 (IL-4)-encoding lentivirus. Study Design: Animal study. Methods: Eighteen adult Sprague-Dawley rats were divided into three groups, all of which sustained a facial nerve gap defect. Group I had reconstruction performed via an IL-4 multichannel bridge, group II had a multichannel bridge with saline placed, and group III had no reconstruction. Results: Quantitative histomorphometric data were assessed 10 weeks after injury. On post hoc analysis, the IL-4 bridge group demonstrated superior regeneration compared to bridge alone on fiber density (mean = 2,380 AE 297 vs. 1,680 AE 441 fibers/mm 2 , P = .05) and latency time (mean = 2.9 ms AE 0.6 ms vs. 3.6 ms AE 0.3 ms, P < .001). There was significantly greater regeneration in the IL-4 bridge group versus unreconstructed defect for total fiber and density measurements (P ≤ .05). Comparison of facial motor-evoked distal latencies between the IL-4 bridge group versus bridge alone revealed significant electrophysiological improvement at week 8 (P = .02). Conclusions: Inflammation has been implicated in a variety of otolaryngologic disorders. This study demonstrates that placement of a multichannel bridge with lentivirus encoding IL-4 improves regenerative outcomes following facial nerve gap injury in rodents. This effect is likely mediated by promotion of an anti-inflammatory environment, and these findings may inform future therapeutic approaches to facial nerve injury.

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Immunohistologic analysis of spontaneous recurrent laryngeal nerve reinnervation in a rat model

Abstract: NA. Laryngoscope, 128:E117-E122, 2018.

Cited by 13 publications

References 38 publications

Automated Quantification of Vocal Fold Motion in a Recurrent Laryngeal Nerve Injury Mouse Model

Automated Quantification of Vocal Fold Motion in a Recurrent Laryngeal Nerve Injury Mouse Model

Main branch of ACN‐to‐RLN for management of laryngospasm due to unilateral vocal cord paralysis

Delivery of Interleukin‐4–Encoding Lentivirus Using Multiple‐Channel Bridges Enhances Nerve Regeneration

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