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Delivery of Interleukin‐4–Encoding Lentivirus Using Multiple‐Channel Bridges Enhances Nerve Regeneration
Author(s) -
Ali S. Ahmed,
Hanks John E.,
Stebbins Aaron W.,
Alkhalili Osama,
Cohen Samantha T.,
Chen Jessica Y.,
Smith Dominique R.,
Dumont Courtney M.,
Shea Lonnie D.,
Hogikyan Norman D.,
Feldman Eva L.,
Brenner Michael J.
Publication year - 2020
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.28629
Subject(s) - bridge (graph theory) , facial nerve , regeneration (biology) , lentivirus , saline , medicine , interleukin , anesthesia , surgery , biology , immunology , cytokine , microbiology and biotechnology , virus , viral disease
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