To examine the effect of the immunosuppressive agent FK506 on the rate of functional recovery of the rat facial nerve after crush injury.
Methods:
Forty rats underwent facial nerve crush injury and were randomly assigned to 4 experimental groups: isotonic sodium chloride solution control, FK binding protein 52 (FKBP-52) antibody control, FK506, and FK506 and FKBP-52 antibody. Rats underwent daily recovery testing from postoperative day 9 until postoperative day 21 by videotaping 3 validated variables in this model: blink reflex return, vibrissial fibrillation loss, and return of vibrissial sweeping symmetry.
Results:
FK506-treated animals demonstrated improved recovery in all 3 variables compared with control animals. The FK506 and FKBP-52 antibody group demonstrated improved recovery of only the return of the blink reflex.
Conclusions:
FK506 accelerated functional recovery of facial nerve function after crush injury. Neuroregeneration was inhibited by FKBP-52 antibody in the rat midface but not the upper face. FK506 may be a viable adjuvant treatment for facial nerve neurapraxic injury.
Get full access to this article
View all access options for this article.
References
1.
CheneyM. Facial Surgery: Plastic and Reconstructive. Baltimore, MD: Williams & Wilkins; 1997
2.
FerriCC, MooreF, BisbyM. Effects of facial nerve injury on mouse motoneurons lacking the p75 low-affinity neurotrophin receptor. J Neurobiol. 1998; 34(1):1-9. 9469614
3.
MostSP. Facial nerve recovery in bcl2 overexpression mice after crush injury. Arch Facial Plast Surg. 2004; 6(2):82-87. 15023794
4.
KobayashiS, KoyamaJ, YokouchiK, FukushimaN, OikawaS, MoriizumiT. Functionally essential neuronal population of the facial motor nucleus. Neurosci Res. 2003; 45(3):357-361. 12631471
5.
SerpeCJ, TetzlaffJ, CoersS, SandersV, JonesK. Functional recovery after facial nerve crush is delayed in severe combined immunodeficient mice. Brain Behav Immun. 2002; 16(6):808-812. 12480509
6.
HadlockTA, HeatonJ, CheneyM, MackinnonS. Functional recovery after facial and sciatic nerve crush injury in the rat. Arch Facial Plast Surg. 2005; 7(1):17-20. 15655169
7.
GuoX, DawsonVL, DawsonTM. Neuroimmunophilin ligands exert neuroregeneration and neuroprotection in midbrain dopaminergic neurons. Eur J Neurosci. 2001; 13(9):1683-1693. 11359520
8.
ButcherSP, HenshallDC, TeramuraY, IwasakiK, SharkeyJ. Neuroprotective actions of FK506 in experimental stroke: in vivo evidence against an antiexcitotoxic mechanism. J Neurosci. 1997; 17(18):6939-6946. 9278529
9.
LyonsWE, GeorgeEB, DawsonTM, SteinerJP, SnyderSH. Immunosuppressant FK506 promotes neurite outgrowth in cultures of PC12 cells and sensory ganglia. Proc Natl Acad Sci U S A. 1994; 91(8):3191-3195. 7512727
10.
MadsenJR, MacDonaldP, IrwinN, et al.Tacrolimus (FK506) increases neuronal expression of GAP-43 and improves functional recovery after spinal cord injury in rats. Exp Neurol. 1998; 154(2):673-683. 9878202
11.
LeeM, DoolabhVB, MackinnonSE, JostSC. FK506 promotes functional recovery in crushed rat sciatic nerve. Muscle Nerve. 2000; 23(4):633-640. 10716776
12.
JostSC, DoolabhVB, MackinnonSE, LeeM, HunterD. Acceleration of peripheral nerve regeneration following FK506 administration. Restor Neurol Neurosci. 2000; 17(1):39-44. 11490076
13.
FengFY, OgdenMA, MyckatynTM, et al.FK506 rescues peripheral nerve allografts in acute rejection. J Neurotrauma. 2001; 18(2):217-229. 11229713
14.
JensenJN, BrennerMJ, TungTH, HunterDH, MackinnonSE. Effect of FK506 on peripheral nerve regeneration through long grafts in inbred swine. Ann Plast Surg. 2005; 54(4):420-427. 15785285
15.
DiazLM, SteeleMH, GuerraAB, et al.The role of topically administered FK506 (tacrolimus) at the time of facial nerve repair using entubulation neurorrhaphy in a rabbit model. Ann Plast Surg. 2004; 52(4):407-413. 15084888
16.
HontanillaB, AubaC, ArcochaJ, GorriaO. Nerve regeneration through nerve autografts and cold preserved allografts using tacrolimus (FK506) in a facial paralysis model: a topographical and neurophysiological study in monkeys. Neurosurgery. 2006; 58(4):768-779. 16575341
17.
FernandezE, PalliniR, MarcheseE, LaurettiL, LaMarcaF. Quantitative, morphological, and somatotopic nuclear changes after facial nerve regeneration in adult rats: a possible challenge to the “no new neurons” dogma. Neurosurgery. 1995; 37(3):456-463. 7501110
18.
StreppelM, AngelovD, Guntinas-LichiusO, et al.Slow axonal regrowth but extreme hyperinnervation of target muscle after suture of the facial nerve in adult rats. Neurobiol Aging. 1998; 19(1):83-88. 9562508
19.
GoldBG, KatohK, Storm-DickersonT. The immunosuppressant FK506 increases the rate of axonal regeneration in rat sciatic nerve. J Neurosci. 1995; 15(11):7509-7516. 7472502
20.
SchreiberSL, CrabtreeGR. The mechanism of action of cyclosporin A and FK 506. Immunol Today. 1992; 13(4):136-142. 1374612
21.
DawsonTM, SteinerJP, DawsonVL, DinermanJ, UhlG, SnyderSH. Immunosuppressant FK506 enhances phosphorylation of nitric oxide synthase and protects against glutamate neurotoxicity. Proc Natl Acad Sci U S A. 1993; 90(21):9808-9812. 7694293
22.
WangHG, PathanN, EthellI, et al.Ca2+ induced apoptosis through calcineurin dephosphorylation of BAD. Science. 1999; 284(5412):339-343. 10195903
23.
GoldBG, DensmoreV, ShouW, MatzukMM, GordonHS. Immunophilin FK506-binding protein 52 (not FK506-binding protein 12) mediates the neurotrophic action of FK506. J Pharmacol Exp Ther. 1999; 289(3):1202-1210. 10336507
24.
AdourKK, KleinJC, BellDN. Trigeminal neurotization of the paralyzed facial musculature: modification of the Lexer-Rosenthal surgical procedure. Arch Otolaryngol. 1979; 105(1):13-16. 760700
25.
GasserRF. The development of the facial nerve in man. Ann Otol Rhinol Laryngol. 1967; 76(1):37-56. 6020340
