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

The Laryngoscope 2020 Dec

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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. Animal study. 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. 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/mm2 , 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). 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. NA Laryngoscope, 2020. © 2020 The American Laryngological, Rhinological and Otological Society, Inc.

Citation

S Ahmed Ali, John E Hanks, Aaron W Stebbins, Osama Alkhalili, Samantha T Cohen, Jessica Y Chen, Dominique R Smith, Courtney M Dumont, Lonnie D Shea, Norman D Hogikyan, Eva L Feldman, Michael J Brenner. Delivery of Interleukin-4-Encoding Lentivirus Using Multiple-Channel Bridges Enhances Nerve Regeneration. The Laryngoscope. 2020 Dec;130(12):2802-2810