Functional and Anatomical Outcomes of Facial Nerve Injury With Application of Polyethylene Glycol in a Rat Model

Abstract

IMPORTANCE Functional and anatomical outcomes after surgical repair of facial nerve injury may be improved with the addition of polyethylene glycol (PEG) to direct suture neurorrhaphy. The application of PEG has shown promise in treating spinal nerve injuries, but its efficacy has not been evaluated in treatment of cranial nerve injuries. OBJECTIVE To determine whether PEG in addition to neurorrhaphy can improve functional outcomes and synkinesis after facial nerve injury. DESIGN, SETTING, AND SUBJECTS In this animal experiment, 36 rats underwent right facial nerve transection and neurorrhaphy with addition of PEG. Weekly behavioral scoring was done for 10 rats for 6 weeks and 14 rats for 16 weeks after the operations. In the 16-week study, the buccal branches were labeled and tissue analysis was performed. In the 6-week study, the mandibular and buccal branches were labeled and tissue analysis was performed. Histologic analysis was performed for 10 rats in a 1-week study to assess the association of PEG with axonal continuity and Wallerian degeneration. Six rats served as the uninjured control group. Data were collected from February 8, 2016, through July 10, 2017. INTERVENTION Polyethylene glycol applied to the facial nerve after neurorrhaphy. MAIN OUTCOMES AND MEASURES Functional recovery was assessed weekly for the 16-and 6-week studies, as well as motoneuron survival, amount of regrowth, specificity of regrowth, and aberrant branching. Short-term effects of PEG were assessed in the 1-week study. RESULTS Among the 40 male rats included in the study, PEG addition to neurorrhaphy showed no functional benefit in eye blink reflex (mean [SEM], 3.57 [0.88] weeks; 95% CI, −2.8 to 1.9 weeks; P = .70) or whisking function (mean [SEM], 4.00 [0.72] weeks; 95% CI, −3.6 to 2.4 weeks; P = .69) compared with suturing alone at 16 weeks. Motoneuron survival was not changed by PEG in the 16-week (mean, 132.1 motoneurons per tissue section; 95% CI, −21.0 to 8.4; P = .13)or6-week(mean, 131.1 motoneurons per tissue section; 95% CI, −11.0 to 10.0; P = .06) studies. Compared with controls, neither surgical group showed differences in buccal branch regrowth at 16 (36.9 motoneurons per tissue section; 95% CI, −14.5 to 22.0; P = .28) or 6 (36.7 motoneurons per tissue section; 95% CI, −7.8 to 18.5; P = .48) weeks or in the mandibular branch at 6 weeks (25.2 motoneurons per tissue section; 95% CI, −14.5 to 15.5; P = .99). Addition of PEG had no advantage in regrowth specificity compared with suturing alone at 16 weeks (15.3% buccal branch motoneurons with misguided projections; 95% CI, −7.2% to 11.0%; P = .84). After 6 weeks, the number of motoneurons with misguided projections to the mandibular branch showed no advantage of PEG treatment compared with suturing alone (12.1% buccal branch motoneurons with misguided projections; 95% CI, −8.2% to 9.2%; P = .98). In the 1-week study, improved axonal continuity and muscular innervation were not observed in PEG-treated rats. CONCLUSIONS AND RELEVANCE Although PEG has shown efficacy in treatin...

Polyethylene glycol (PEG) and other bioactive solutions with neurorrhaphy for rapid and dramatic repair of peripheral nerve lesions by PEG-fusion

“…Whether the labeled axons ever reinnervated the correct or incorrect muscle is never assessed. Brown et al (2018) conclude that "polyethylene glycol fusion has shown efficacy in the surgical repair of spinal nerve injuries, but this finding was not replicated in facial nerve injury repair." However, Brown et al (2018) almost-certainly did not induce PEG-fusion repair because of technical issues including use of: 1) 500mM PEG solution rather than a 50% w/w (500millimolal) solution, 2) isotonic rather than hypotonic conditioning solutions, and/or 3) an unstated solution of MB.…”

“…Brown et al (2018) conclude that "polyethylene glycol fusion has shown efficacy in the surgical repair of spinal nerve injuries, but this finding was not replicated in facial nerve injury repair." However, Brown et al (2018) almost-certainly did not induce PEG-fusion repair because of technical issues including use of: 1) 500mM PEG solution rather than a 50% w/w (500millimolal) solution, 2) isotonic rather than hypotonic conditioning solutions, and/or 3) an unstated solution of MB. Furthermore, they performed no intraoperative assays to demonstrate successful PEG-fusion, i.e., to confirm that they successfully PEG-fused proximal and distal ends of some axons at the lesion site.…”

“…Incorrect understandings of the mechanism of action of PEG-fusion, how to evaluate intraand post-operative success, and unwarranted conclusions about negative outcomes are problems that must be addressed as they could impede progress and innovation of a potentially important advance in clinical management of patients with peripheral nerve injuries. Problems with misunderstandings or not following the standard protocol (especially intraoperative testing to confirm an initial successful PEG-fusion), its rationale, and subsequent misinterpretation of tracer labels are illustrated by two recent papers by Robinson and Madison (2016) and Brown et al (2018). Robinson and Madison (2016) report inappropriate specificity of outgrowth regeneration after two-tracer-labeling of a motor branch of a PEG-fused femoral nerve at 8w (56d) PO.…”

Tailoring synthetic polymeric biomaterials towards nerve tissue engineering: a review

“…At variance with the above-mentioned studies, Robinson et al reported that PEG fusion disrupted the beneficial trophic influence of muscle on motor neuron reinnervation accuracy in rats [121]. Moreover, Brown et al reported that PEG did not exert beneficial effects in the regeneration of facial nerve injury in rats [122].…”

Characterization of Chitosan and Polyethylene glycol Blend Film

“…Polyethylene glycol (PEG), a linear polymer derived from ethylene oxide, finds a broad range of application in both biomedical and industrial sections [19][20][21][22]. It is regarded as one of the Egypt.J.Chem.…”