Original ArticleThe Role of Topically Administered FK506 (Tacrolimus) at the Time of Facial Nerve Repair Using Entubulation Neurorrhaphy in a Rabbit ModelDiaz, L Michael MD*; Steele, Matthew H. MD*; Guerra, Aldo B. MD†; Aubert, Fred E. MD*; Sloop, Gregory D. MD‡; Diaz, Hebe A. MD§; Metzinger, Rebecca C. MD¶; Blake, Dianne B. PhD¶; Delaune, Christie L. BS∥; Metzinger, Stephen E. MD*Author Information From the Department of †Surgery and ‡Pathology, the **Division of Plastic Surgery, Department of Otolaryngology, and the ∥Gene Therapy Program, *LSU Health Sciences Center; and the ¶Department of Ophthalmology, §Tulane University Medical School, New Orleans, LA. Received April 24, 2003, and accepted for publication, after revision, August 9, 2003. Supported and accepted by the LSU Health Science Center-New Orleans, Institutional Animal Care and Use Committee (protocol no. 1076). Funded by a grant from AO/North America. Presented at the Louisiana Society of Plastic and Reconstructive Surgeons meeting, New Orleans, LA, January 25, 2003. Reprints: Stephen E. Metzinger, MD, Associate Professor of Surgery, Division of Plastic Surgery, Department of Otolaryngology-Head and Neck Surgery, Co-Program Director, Division of Plastic Surgery, LSU Health Sciences Center, New Orleans, LA. E-mail: [email protected] Annals of Plastic Surgery: April 2004 - Volume 52 - Issue 4 - p 407-413 doi: 10.1097/01.sap.0000107780.37285.6d Buy Metrics AbstractIn Brief Peripheral facial nerve palsy is a common sequela of traumatic craniofacial injury, often resulting in dramatic and sometimes permanent functional deficits. Exogenous agents and methods of repair that accelerate axonal regeneration would be of great benefit to the multitude of patients with facial nerve injuries. The objective of this study was to evaluate the effect of FK506 at the time of facial nerve repair using entubulation neurorrhaphy, and to compare entubulation neurorrhaphy versus interposition autograft in critical facial nerve gap defects. The study design was a prospective, randomized, blinded animal study with a control group. Twenty-five New Zealand White rabbits were assigned to 4 experimental groups and a control group. The buccal branch of the facial nerve was used in all procedures. Group 1 was the control group. Rabbits in group 2 underwent sham surgery. Group 3 was an interposition autograft group in which a 6-mm segment of nerve was transacted, flipped, and followed by epineural repair. Groups 4 and 5 underwent transection followed by entubulation neurorrhaphy with topical administration of either a carrier molecule (group 4) or an FK506 carrier molecule (group 5). Outcome measures included daily subjective assessment of upper lip movement; electromyographic studies at weeks 3, 5, and 8 postoperatively; and blinded quantitative histomorphometric evaluation after 8 weeks. All rabbits in all groups were noted to have spontaneous movement after 8 weeks, with 1 rabbit in group 5 obtaining the highest functional score among all study groups. Electrophysiologic studies showed polyphasic potentials, indicating reinnervation in 1 rabbit in group 5. Histomorphometric examination of group 5 rabbits revealed a similar cross-sectional area distal to transection and remyelination. Other groups showed decreased cross-sectional area and/or incomplete remyelination distal to the transection. FK506 applied topically at the time of facial nerve repair using entubulation neurorrhaphy demonstrated superior results in nerve regeneration versus entubulation neurorrhaphy carrier protein alone, and interposition autograft. In a rabbit facial nerve gap model, interposition autografting was compared to entubulation neurorrhaphy with or without FK506 in the polyglycolic acid tubing. The animals treated with FK506 showed superior reinnervation in both functional and histomorphometric measures. © 2004 Lippincott Williams & Wilkins, Inc.