Development and characterisation of an experimental recurrent laryngeal nerve injury model for the study of viral gene therapy

Abstract

AbstractObjectives:To develop and characterise an experimental model of recurrent laryngeal nerve injury for the study of viral gene therapy.Methods:Twenty rats underwent unilateral recurrent laryngeal nerve injury. After vocal fold mobility was observed, larynges were serially sectioned, and immunohistochemical techniques were employed to stain for neurofilament and motor endplates in order for a blinded investigator to determine the percentage of nerve–endplate contact, as a histological indicator of an intact neuromuscular connection.Results:All animal procedures resulted in complete, ipsilateral vocal fold paralysis that recovered by three weeks. The mean nerve–endplate contact percentage was 11.6 per cent at one week, 53.9 per cent at two weeks, 88.6 per cent at three weeks, 81.7 per cent at four weeks and 86.6 per cent at five weeks. The differences between results at week one and week three were statistically significant (p < 0.01). The mean nerve–endplate contact percentage on the control side was 86.8 per cent.Conclusions:There was a dramatic, measurable decrease in nerve–endplate contact percentage following crush injury to the recurrent laryngeal nerve. Spontaneous recovery was observed by three weeks post-injury. This model will be used to investigate the potential therapeutic role of viral gene therapy for the treatment of recurrent laryngeal nerve injury.