title: Neuregulin-1 released by biodegradable gelatin hydrogels can accelerate facial nerve regeneration and functional recovery of traumatic facial nerve palsy.
abstract: OBJECTIVE
  Neuregulin-1 is an essential axoglial signal required for peripheral nerve development, and evidence that neuregulin-1 is also required for effective nerve repair is growing. In this study, the effects of neuregulin-1-impregnated gelatin hydrogels on nerve regeneration and functional recovery after anastomosis of the facial nerve were investigated in a rat model of traumatic facial nerve paralysis.
  
  
  METHODS
  Twenty-four adult male rats underwent complete resection of the facial nerve trunk, followed by end-to-end anastomosis with epineural sutures. The animals were then randomly allocated to one of three treatment groups (eight rats/group): no additional intervention (Group I), single-shot injection of neuregulin-1 into the epineurium of the facial nerve at the suture sites (Group II), or implantation of a hydrogel impregnated with neuregulin-1 at the injury site (Group III). After surgery, mimetic muscle movements were evaluated weekly. Eight weeks after surgery, the mimetic muscles were injected with a neural tracer (1,10-dioctadecyl-3,3,30,30-tetramethylindocarbocyanin perchlorate, DiI). Retrograde-labeled neurons were counted in the facial nuclei, and facial nerve specimens were stained with toluidine blue for histological examination of axon density.
  
  
  RESULTS
  Group III exhibited significantly faster recovery of mimetic muscle function, a higher density of large-diameter axons (>5 μm) in the facial nerve, and greater numbers of retrogradely labeled neurons in the ipsilateral facial nucleus compared with Groups I and II.
  
  
  CONCLUSIONS
  Continuous release of neuregulin-1 from impregnated gelatin hydrogels can accelerate facial nerve regeneration.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Hokkaido, Kita-15 Nishi-7, Kita-Ku, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Yasui
authors.affiliation: Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Hokkaido, Kita-15 Nishi-7, Kita-Ku, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Hokkaido, Kita-15 Nishi-7, Kita-Ku, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Shichinohe
authors.affiliation: Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Hokkaido, Kita-15 Nishi-7, Kita-Ku, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Funayama
authors.affiliation: Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Hokkaido, Kita-15 Nishi-7, Kita-Ku, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Oyama
authors.affiliation: Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Hokkaido, Kita-15 Nishi-7, Kita-Ku, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Hokkaido, Kita-15 Nishi-7, Kita-Ku, Sapporo, Hokkaido 060-8638, Japan. Electronic address: hfuru@med.hokudai.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
mesh_terms: D020341:Absorbable Implants / Q000706:statistics & numerical data*; D000714:Anastomosis, Surgical; D000818:Animals; D004195:Disease Models, Animal; D005152:Facial Muscles / Q000187:drug effects / Q000294:innervation; D005154:Facial Nerve / Q000187:drug effects; D020220:Facial Nerve Injuries / Q000188:drug therapy* / Q000601:surgery*; D005158:Facial Paralysis / Q000188:drug therapy* / Q000601:surgery; D020100:Hydrogels / Q000494:pharmacology; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D020890:Neuregulin-1 / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D018570:Risk Assessment; D013536:Suture Techniques; D016896:Treatment Outcome
chemical_list: D020100:Hydrogels; D020890:Neuregulin-1
keywords: Biodegradable gelatin hydrogels; Facial nerve regeneration; Facial palsy scores; Neuregulin-1 (NRG1); Toluidine blue; Tracer study