Literature DB >> 31219545

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

S Ahmed Ali1, John E Hanks1, Aaron W Stebbins1,2, Samantha T Cohen1, Daniel A Hunter3, Alison K Snyder-Warwick3, Susan E Mackinnon3, Robbi A Kupfer1, Norman D Hogikyan1, Eva L Feldman2, Michael J Brenner1.   

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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Year:  2019        PMID: 31219545      PMCID: PMC6587147          DOI: 10.1001/jamafacial.2019.0398

Source DB:  PubMed          Journal:  JAMA Facial Plast Surg        ISSN: 2168-6076            Impact factor:   4.611


  45 in total

1.  Functional recovery following peripheral nerve injury in the transgenic Thy1-GFP rat.

Authors:  Stephen W P Kemp; Peter D Phua; Krisanne N Stanoulis; Matthew D Wood; Edward H Liu; Tessa Gordon; Gregory H Borschel
Journal:  J Peripher Nerv Syst       Date:  2013-09       Impact factor: 3.494

2.  Reduction of oligodendrocyte myelin glycoprotein expression following facial nerve transection.

Authors:  Yoshihisa Koyama; Toshihiro Fujiwara; Tateki Kubo; Koichi Tomita; Kenji Yano; Ko Hosokawa; Masaya Tohyama
Journal:  J Chem Neuroanat       Date:  2008-08-31       Impact factor: 3.052

3.  C3 transferase gene therapy for continuous conditional RhoA inhibition.

Authors:  Claire-Anne Gutekunst; Jack K Tung; Margaret E McDougal; Robert E Gross
Journal:  Neuroscience       Date:  2016-10-13       Impact factor: 3.590

4.  Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP.

Authors:  G Feng; R H Mellor; M Bernstein; C Keller-Peck; Q T Nguyen; M Wallace; J M Nerbonne; J W Lichtman; J R Sanes
Journal:  Neuron       Date:  2000-10       Impact factor: 17.173

5.  Immunohistological intensity measurements as a tool to assess sarcolemma-associated protein expression.

Authors:  V Arechavala-Gomeza; M Kinali; L Feng; S C Brown; C Sewry; J E Morgan; F Muntoni
Journal:  Neuropathol Appl Neurobiol       Date:  2009-11-25       Impact factor: 8.090

6.  Topical axonal transport blocker vincristine prevents nerve injury-induced spinal neuron sensitization in rats.

Authors:  M L Sotgiu; G Biella; L Firmi; V Pasqualucci
Journal:  J Neurotrauma       Date:  1998-12       Impact factor: 5.269

7.  Depressor labii inferioris resection: an effective treatment for marginal mandibular nerve paralysis.

Authors:  G Hussain; R T Manktelow; L R Tomat
Journal:  Br J Plast Surg       Date:  2004-09

8.  Rodent facial nerve recovery after selected lesions and repair techniques.

Authors:  Tessa A Hadlock; Jeffrey Kowaleski; David Lo; Susan E Mackinnon; James T Heaton
Journal:  Plast Reconstr Surg       Date:  2010-01       Impact factor: 4.730

9.  The effect of electrical and mechanical stimulation on the regenerating rodent facial nerve.

Authors:  Tessa Hadlock; Robin Lindsay; Colin Edwards; Christopher Smitson; Julie Weinberg; Christopher Knox; James T Heaton
Journal:  Laryngoscope       Date:  2010-06       Impact factor: 3.325

Review 10.  Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration.

Authors:  Trisha R Stankiewicz; Daniel A Linseman
Journal:  Front Cell Neurosci       Date:  2014-10-07       Impact factor: 5.505

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