Delivery Of Interleukin-4-Encoding Lentivirus Using Multiple-Channel Bridges Enhances Nerve Regeneration

LARYNGOSCOPE(2020)

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摘要
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 +/- 297 vs. 1,680 +/- 441 fibers/mm(2), P = .05) and latency time (mean = 2.9 ms +/- 0.6 ms vs. 3.6 ms +/- 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.Level of Evidence NA Laryngoscope, 2020
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关键词
Facial nerve injury, axotomy, motoneuron regeneration, interleukin-4, anti-inflammatory
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