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

Laryngoscope. 2020 Dec;130(12):2802-2810. doi: 10.1002/lary.28629. Epub 2020 Mar 27.

Abstract

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/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).

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.

Keywords: Facial nerve injury; anti-inflammatory; axotomy; interleukin-4; motoneuron regeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Facial Nerve Injuries / surgery*
  • Interleukin-4*
  • Lentivirus
  • Nerve Regeneration / physiology*
  • Plastic Surgery Procedures / methods*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Interleukin-4