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Original Investigation
AAFPRS Research Award Winner
June 20, 2019

Comparison of Myelin-Associated Glycoprotein With Vincristine for Facial Nerve Inhibition After Bilateral Axotomy in a Transgenic Thy1-Gfp Rat Model

Author Affiliations
  • 1Department of Otolaryngology–Head & Neck Surgery, Michigan Medicine, Ann Arbor
  • 2Department of Neurology, Michigan Medicine, Ann Arbor
  • 3Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri
JAMA Facial Plast Surg. 2019;21(5):426-433. doi:10.1001/jamafacial.2019.0398
Key Points

Question  What is the neuroinhibitory potential of myelin-associated glycoprotein in comparison with vincristine, as measured via quantification of fluorescent intensity of the facial nerve after an axotomy injury?

Findings  In this laboratory experiment on 12 rats transgenic for the Thy-1 Gfp gene, myelin-associated glycoprotein significantly reduced fluorescent intensity in comparison with saline at weeks 3, 4, and 5 after an initial injury. Myelin-associated glycoprotein demonstrated similar intensity results as vincristine at weeks 4 and 5.

Meaning  These findings suggest that myelin-associated glycoprotein may have potential as a specific neuroinhibitor for patients with lower facial asymmetry after facial nerve injury.

Abstract

Importance  Aberrant synkinetic movement after facial nerve injury can lead to prominent facial asymmetry and resultant psychological distress. The current practices of neuroinhibition to promote greater facial symmetry are often temporary in nature and require repeated procedures.

Objective  To determine whether myelin-associated glycoprotein (MAG), a specific neuroinhibitor, can prevent neuroregeneration with efficacy comparable with that of vincristine, a well-established neurotoxin.

Design, Setting, and Participants  Rats transgenic for Thy-1 cell surface antigen–green fluorescent protein (Thy1-Gfp) were randomized into 3 groups. Each rat received bilateral crush axotomy injuries to the buccal and marginal mandibular branches of the facial nerves. The animals received intraneural injection of saline, MAG, or vincristine.

Main Outcomes and Measures  The animals were imaged via fluorescent microscopy at weeks 1, 3, 4, and 5 after surgery. Quantitative fluorescent data were generated as mean intensities of nerve segments proximal and distal to the axotomy site. Electrophysiological analysis, via measurement of compound muscle action potentials, was performed at weeks 0, 3, 4, and 5 after surgery.

Results  A total of 12 rats were included in the study. Administration of MAG significantly reduced fluorescent intensity of the distal nerve in comparison with the control group at week 3 (mean [SD], MAG group: 94 [11] intensity units vs control group: 130 [11] intensity units; P < .001), week 4 (MAG group: 81 [19] intensity units vs control group: 103 [9] intensity units; P = .004), and week 5 (MAG group: 76 [10] intensity units vs control group: 94 [10] intensity units; P < .001). In addition, rats treated with MAG had greater fluorescent intensity than those treated with vincristine at week 3 (mean [SD], MAG group: 94 [11] intensity units vs vincristine group: 76 [6] intensity units; P = .03), although there was no significant difference for weeks 4 and 5. At week 5, both MAG and vincristine demonstrated lower distal nerve to proximal nerve intensity ratios than the control group (control group, 0.94; vs MAG group, 0.82; P = .01; vs vincristine group; 0.77; P < .001). There was no significant difference in amplitude between the experimental groups at week 5 of electrophysiological testing.

Conclusions and Relevance  Lower facial asymmetry and synkinesis are common persistent concerns to patients after facial nerve injury. Using the Thy1-Gfp rat, this study demonstrates effective inhibition of neuroregeneration via intraneural application of MAG in a crush axotomy model, comparable with results with vincristine. By potentially avoiding systemic toxic effects of vincristine, MAG demonstrates potential as an inhibitor of neural regeneration for patients with synkinesis.

Level of Evidence  NA.

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