Transgenic mouse facial nerve model of synkinesis

Abstract

HypothesisOur central hypothesis is that inhibition of Schwann cell de-differentiation, in the post-injury setting, will reduce synkinesis and improve facial muscle function BackgroundNo therapies exist to improve the accuracy of facial nerve regeneration. Following peripheral nerve injury, adult reactive Schwann cells de-differentiate and express glial fibrillary acidic protein (GFAP); suggesting that reactive Schwann cells impact axonal regeneration precision. MethodsTransgenic GFAP-thymidine kinase (TK) mouse model was employed, allowing selective downregulation of reactive GFAP expressing Schwann cells on exposure of 7 day osmotic pump delivery of ganciclovir. Adult female transgenic GFAP-TK mice had right facial nerve transected and then immediately repaired with tissue glue, they then either were treated with saline or ganciclovir (GCV). At 6 weeks post-injury, mice were exposed to random air puffs events while high speed videography recorded whisker and eye movement. MatLab code video processing with publicly available BIOTACT algorithm automatically tracked whiskers. ResultsWhisker velocity was calculated using binning statistical analysis. Saline treated animals confirmed our models ability to detect aberrant movement such that intact (left) facial nerves caused whisker protraction, while repaired (right) facial nerves had retraction. Administration of GCV increased whisker retraction compared to saline. GCV did not impact intact animal whisker movement compared to repaired whiskers. ConclusionsInhibition of reactive Schwann cell proliferation appears to worse the degree of synkinesis, providing important insight into a potential therapeutic target for facial nerve injury.