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Accelerated rehabilitation following facial nerve injury presents unique clinical challenges. This study evaluates the therapeutic effects of concentrated growth factor (CGF) on facial nerve recovery in a rabbit model and on RSC96 Schwann cells. Characterization of the CGF membrane (CGFM) revealed a three-dimensional fibrin network with embedded platelets, and representative growth factors, including TGF-β1, PDGF-BB, IGF-1, bFGF, and VEGF, were detected. In vivo , the Crush + CGFM group exhibited enhanced axon and myelin regeneration, increased Schwann cell proliferation, and improved facial nerve function compared to the Crush group. In vitro , CGF treatment significantly promoted the proliferation and migration of RSC96 cells and facilitated axon elongation in NG108-15 cells compared to controls. Mechanistically, CGF treatment led to a significant increase in PDGFRβ phosphorylation. Inhibition of this pathway with SU16f decreased Schwann cell activity and hindered overall nerve rehabilitation. These results underscore CGF's potential to accelerate nerve repair by promoting axon and myelin regeneration and enhancing Schwann cell biological activity, with the PDGFRβ pathway playing a crucial regulatory role. This study highlights CGF as a promising therapeutic strategy for improving facial nerve rehabilitation.

Severe axonal damage in the peripheral nerves results in retrograde degeneration towards the central side, leading to neuronal cell death, eventually resulting in incomplete axonal regeneration and functional recovery. Therefore, it is necessary to evaluate the facial nerve nucleus in models of facial paralysis, and investigate the efficacy of treatments, to identify treatment options for severe paralysis. Consequently, we aimed to examine the percentage of facial nerve cell reduction and the extent to which intratympanic administration of a basic fibroblast growth factor (bFGF) inhibits neuronal cell death in a model of severe facial paralysis. A severe facial paralysis model was induced in Hartley guinea pigs by freezing the facial canal. Animals were divided into two groups: one group was treated with gelatin hydrogel impregnated with bFGF (bFGF group) and the other was treated with gelatin hydrogel impregnated with saline (control group). Facial movement scoring, electrophysiological testing, and histological assessment of facial neurons were performed. The freezing-induced facial paralysis model showed a facial neuronal cell death rate of 29.0%; however, bFGF administration reduced neuronal cell death to 15.8%. Facial movement scores improved in the bFGF group compared with those in the control group. Intratympanic bFGF administration has a protective effect on facial neurons in a model of severe facial paralysis. These findings suggest a potential therapeutic approach for treating patients with refractory facial paralysis. Further studies are required to explore the clinical applicability of this treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Iwata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Rosuvastatin is an antihyperlipidemic statin group pharmacological agent with antioxidant, neuroprotective, and anti-inflammatory effects. In this study, we aimed to examine the functional, electrophysiological, and histopathological effects of rosuvastatin or in combination with corticosteroids on facial nerve regeneration in rats with traumatic peripheral facial paralysis (PFP)., Methods: PFP was induced in 28 female Sprague Dawley rats that we divided into 4 groups: group 1, control group; group 2, methylprednisolone group; group 3, rosuvastatin group; group 4, rosuvastatin and methylprednisolone group. Electrophysiological, functional, and histopathological examinations were performed before and after the medications., Results: Electrophysiological threshold values of group 3 and group 4 were found to be significantly lower than the control group on day 21 after treatment ( P  = .002, P  = .001; P  < .01).In the histopathological evaluation, axonal degeneration, macrovacuolization, and vascular congestion levels were compared between the groups, and a statistically significant difference was observed in group 4 compared to the control group. The recovery time of the eye corneal reflex was found to be significantly higher in the control group than in groups 3 and 4 when comparing postoperative day 1 to day 7 and postoperative day 1 to day 14., Conclusion: Rosuvastatin, especially when combined with methylprednisolone was found to significantly increase the facial nerve electrophysiological, functional, and histopathological recovery in injury-induced traumatic PFP., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Corticosteroid therapy is commonly recommended for acute facial nerve weakness; however, its effectiveness in treating traumatic nerve injuries remains controversial. This study investigated the functional recovery and cellular effects of systemic dexamethasone administration after facial nerve injury., Methods: C57BL/6 mice were assigned to two groups by intraperitoneal injection: the phosphate-buffered saline group and the dexamethasone group. Facial nerve crush injury was induced, followed by the functional grading of recovery. Cellular effects were investigated using transmission electron microscopy, flow cytometry, immunofluorescence, and intravital imaging., Results: Macrophage infiltration into the facial nerves was significantly inhibited by systemic dexamethasone administration. However, dexamethasone group slightly delayed the functional recovery of the facial nerve compared to the PBS group. In addition, the morphological changes in the nerve were not significantly different between the two groups at 14 days post-injury. Macrophage migration analysis in the intravital imaging also showed no difference between groups., Conclusions: In summary, systemic dexamethasone successfully inhibited leukocyte infiltration; however, functional recovery was delayed compared to the PBS control group. Clinically, these findings indicate that more evidence and research are required to use steroid pulse therapy for the treatment of traumatic facial nerve injuries., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Objective: This study aimed to evaluate the efficacy of adjunct low-frequency pulse electrical stimulation alongside dexamethasone in the treatment of facial nerve paralysis and its subsequent effects on facial nerve function and electromyographic parameters. With the aim of addressing a knowledge gap in the field, this research provides valuable insights into the potential benefits of combining these treatments and their impact on clinical outcomes, facial nerve functionality, and electromyographic dynamics., Methods: A cohort of 66 patients with facial nerve paralysis treated at our institution between April 2018 and November 2021 were randomly assigned to either an observation (n=33) or an experimental group (n=33). The observation group received standard pharmacotherapy, including Western medications and Daqinjiao decoction, along with dexamethasone. The experimental group was administered low-frequency pulse electrical stimulation in addition to the observation group's regimen. Outcomes assessed were clinical efficacy, facial nerve paralysis scoring, facial nerve functional scoring and indices, electromyographic latency, amplitude ratios between affected and unaffected sides, as well as any adverse events., Results: The experimental group demonstrated a significant improvement over the observation group in clinical treatment outcomes, facial nerve paralysis scores, and facial nerve function scores (P < .05 for all). Furthermore, electromyographic analysis revealed shorter latency periods and greater amplitude ratios in the experimental group's facial muscles post-treatment (P < .05). No significant difference was observed in the incidence of adverse reactions between the two groups (P > .05)., Conclusion: The integration of low-frequency pulse electrical stimulation with dexamethasone therapy significantly ameliorates the severity of facial nerve paralysis, enhances facial nerve function, and improves electromyographic signals in facial muscles without increasing adverse effects. These findings support the clinical value and safety of this combined treatment approach for facial nerve paralysis, suggesting its suitability for broader clinical application. These results suggest that this combined treatment approach holds promise for broader clinical application, potentially providing a more effective and safer therapeutic option for patients with facial nerve paralysis. Implementing this approach in clinical practice may lead to improved treatment outcomes, better functional recovery, and enhanced quality of life for affected individuals.

Background: Ebselen is a neuroprotective drug that protects cellular components from oxidative damage by modulating enzymatic cofactors, metalloproteins, gene expression, antioxidant-anti-inflammatory effects, and immunological systems. Our goal was to compare the efficacy of Ebselen and methylprednisolone on rat facial nerve crush injury., Methods: Thirty healthy male Wistar rats (mean weight of 245 g) were used in this study. The rats were randomly divided into four groups: Group 1 (ebselen group), Group 2 (methylprednisolone group), Group 3 (control group), and Group 4 (sham group (the right side of the control group)). Except for the sham group, all groups had their left facial nerve crushed. Three weeks after surgery, prospective functional, histologic, and electrophysiologic recovery was reported., Results: The ebselen group and methylprednisolone group had similar and more significant recovery at Nerve Excitability Thresholds (NET) at the end of three weeks. These groups also showed similar features in terms of histopathological parameters such as axonal degeneration, vascular congestion, axon diameter, and myelin thickness. Except for the macrovacuolization parameter, both showed statistically better results than the control group. Although there was an earlier improvement in the whiskers and blink tests in the ebselen group compared to the methylprednisolone and control groups, complete recovery was observed in all groups on the 21st day., Conclusion: Ebselen was found to be similarly effective to methylprednisolone in nerve regeneration in a rat model of experimental facial nerve crush. Considering that methylprednisolone has serious systemic side effects, ebselen may be a good alternative.

Aim: This study aimed to evaluate the effect of systemic/local use of melatonin and glatiramer acetate on regeneration in traumatic nerve injury models., Materials and Methods: A total of 42 male Wistar albino rats were randomly divided into 6 groups: healthy control (Group 1), injured control (Group 2), local melatonin (Group 3), systemic melatonin (Group 4), local glatiramer acetate (Group 5), and systemic glatiramer acetate (Group 6). In all groups, electromyography recordings of the facial nerve were obtained after surgery and before sacrifice, and the damaged nerve region was histopathologically examined after sacrifice., Results: In the electrophysiological evaluation, the control group had the greatest decrease in amplitude and extension in latency time following surgery than the treatment groups. Furthermore, a significant decrease in the degenerative axon count, edematous areas, and fibrotic areas as well as a significant increase in axonal surface areas was observed in all the treatment groups compared with the damage control group., Conclusions: Although both glatiramer acetate and melatonin are beneficial in regeneration in traumatic facial nerve injuries, it can be concluded that systemic use of melatonin can yield more positive results than glatiramer acetate and local use of both two drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Botulinum toxin is an effective treatment for hemifacial spasm in elderly patients. However, some patients do not tolerate the side effects and frequency of botulinum toxin treatments., Objectives: The purpose of this study was to evaluate the characteristics and outcomes of a cohort of elderly patients referred by neurologists for surgical decompression of the facial nerve following botulinum toxin treatment., Methods: In a prospective cohort study, logistic regression was used to detect potential predictors of spasm-freedom after surgical decompression of the facial nerve in elderly patients that received ≤8 and >8 botulinum toxin treatments for hemifacial spasm before surgery. Age, sex, side, preoperative symptom duration, and preoperative botulinum toxin treatment were assessed as potential predictors of spasm-freedom at last follow-up., Results: Of 76 elderly patients with hemifacial spasm treated with botulinum toxin and microvascular decompression, with at least 2-years of follow-up (median, 44.5 months), 84.2% were spasm-free at last follow-up. Age (P = 0.38), sex (P = 0.59), side (P = 0.15), preoperative symptom duration (P = 0.7), and number of preoperative botulinum toxin treatments (P = 0.3) were not predictors of long-term spasm-freedom. Permanent ipsilateral hearing loss was the most frequent complication (3.9%)., Conclusion: This study provides evidence that elderly patients can undergo botulinum toxin treatment for hemifacial spasm without compromising their likelihood of achieving spasm-freedom with future surgical decompression. Therefore, surgical decompression of the facial nerve is an effective therapy for elderly patients with hemifacial spasm refractory to botulinum toxin., (© 2024 International Parkinson and Movement Disorder Society.)

Purpose: Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few clinical studies on ciprofol. We sought to examine the safety and efficacy of ciprofol use for general anesthesia in neurosurgical individuals undergoing neurosurgical surgery with intraoperative neurophysiological monitoring (IONM)., Patients and Methods: This single-center, non-inferiority, single-blind, randomized controlled trial was conducted from September 13, 2022 to September 22, 2023. 120 patients undergoing elective microvascular decompression surgery (MVD) with IONM were randomly assigned to receive either ciprofol or propofol. The primary outcome of this study was the amplitude of intraoperative compound muscle action potential decline, and the secondary outcome included the indexes related to neurophysiological monitoring and anesthesia outcomes., Results: The mean values of the primary outcome in the ciprofol group and the propofol group were 64.7±44.1 and 53.4±35.4, respectively. Furthermore, the 95% confidence interval of the difference was -25.78 to 3.12, with the upper limit of the difference being lower than the non-inferiority boundary of 6.6. Ciprofol could achieve non-inferior effectiveness in comparison with propofol in IONM of MVD. The result during anesthesia induction showed that the magnitude of the blood pressure drop and the incidence of injection pain in the ciprofol group were significantly lower than those in the propofol group (P<0.05). The sedative drug and norepinephrine consumption in the ciprofol group was significantly lower than that in the propofol group (P<0.05)., Conclusion: Ciprofol is not inferior to propofol in the effectiveness and safety of IONM and the surgical outcome. Concurrently, ciprofol is more conducive to reducing injection pain and improving hemodynamic stability, which may be more suitable for IONM-related surgery, and has a broad application prospect., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhu et al.)

Background: The pathway by which drugs are injected subcutaneously behind the ear to act on the inner ear has not been fully elucidated., Objectives: To compare the uptake of gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (Dex) in the cochlea and facial nerve of rats following different administrations., Materials and Methods: Magnetic resonance imaging was applied to observe the distribution of Gd-DTPA in the facial nerve and inner ear. We observed the uptake of Dex after it was injected with different methods., Results: Images of the intravenous (IV) and intramuscular (IM) groups showed that the bilateral cochlea of the rat was visualized almost simultaneously. While in the left post-auricular (PA) injection group, it was asynchronous. The maximum accumulation ( C max ) of the Gd in the left facial nerve of the PA group (35.406 ± 5.32) was substantially higher than that of the IV group (16.765 ± 3.7542) ( p  < .01)., Conclusions: Compared with systemic administration, PA has the advantages of long Gd and Dex action time and high accumulation concentration to treat facial nerve diseases., Significance: The distribution of Gd and Dex in the inner ear and facial nerve of rats following PA injection might be unique.

(1) Objective: In order to evaluate the effect of a pre-induced mesenchymal stem cell (MSC)-coated cellulose/collagen nanofibrous nerve conduit on facial nerve regeneration in a rat model both in vitro and in vivo. (2) Methods: After fabrication of the cellulose/collagen nanofibrous conduit, its lumen was coated with either MSCs or pre-induced MSCs. The nerve conduit was then applied to the defective main trunk of the facial nerve. Rats were randomly divided into three treatment groups (n = 10 in each): cellulose/collagen nanofiber (control group), cellulose/collagen nanofiber/MSCs (group I), and cellulose/collagen nanofiber/pre-induced MSCs (group II). (3) Results Fibrillation of the vibrissae of each group was observed, and action potential threshold was compared 8 weeks post-surgery. Histopathological changes were also observed. Groups I and II showed better recovery of vibrissa fibrillation than the control group. (4) Conclusions: Group II, treated with the pre-induced MSC-coated cellulose/collagen nanofibrous nerve conduit, showed the highest degree of recovery based on functional and histological evaluations.

Nerve growth factor (NGF) is important for peripheral nerve regeneration. However, its short half-life and rapid diffusion in body fluids limit its clinical efficacy. Collagen has favorable biocompatibility and biodegradability, and weak immunogenicity. Because it possesses an NGF binding domain, we cross-linked heparin to collagen tubes to construct nerve guidance conduits for delivering NGF. The conduits were implanted to bridge a facial nerve defect in rats. Histological and functional analyses were performed to assess the effect of the nerve guidance conduit on facial nerve regeneration. Heparin enhanced the binding of NGF to collagen while retaining its bioactivity. Also, the nerve guidance conduit significantly promoted axonal growth and Schwan cell proliferation at 12 weeks after surgery. The nerve regeneration and functional recovery outcomes using the nerve guidance conduit were similar to those of autologous nerve grafting. Therefore, the nerve guidance conduit may promote safer nerve regeneration., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

In Bell's palsy, electrodiagnosis by electroneurography (ENoG) is widely used to predict a patient's prognosis. The therapeutic options for patients with poor prognostic results remain controversial. Here, we investigated whether early intervention with intratympanic steroid therapy (ITST) is an effective treatment for Bell's palsy patients with poor electrodiagnostic test results (≤ 10% electroneurography value). Patients in the concurrent ITST group (n = 8) received the standard systemic dose of prednisolone (410 mg total) and intratympanic dexamethasone (16.5 mg total) and those in the control group (n = 21) received systemic prednisolone at the standard dose or higher (average dose, 605 ± 27 mg). A year after onset, the recovery rate was higher in the ITST group than in the control group (88% vs 43%, P = 0.044). The average House-Brackmann grade was better in the concurrent ITST group (1.13 ± 0.13 vs 1.71 ± 0.16, P = 0.035). Concurrent ITST improves the facial nerve outcome in patients with poor electroneurography test results, regardless of whether equivalent or lower glucocorticoid doses were administered. This may be ascribed to a neuroprotective effect of ITST due to a higher dose of steroid reaching the lesion due to dexamethasone transfer in the facial nerve.

The pontine Kölliker-Fuse nucleus (KFn) is a core nucleus of respiratory network that mediates the inspiratory-expiratory phase transition and gates eupneic motor discharges in the vagal and hypoglossal nerves. In the present study, we investigated whether the same KFn circuit may also gate motor activities that control the resistance of the nasal airway, which is of particular importance in rodents. To do so, we simultaneously recorded phrenic, facial, vagal and hypoglossal cranial nerve activity in an in situ perfused brainstem preparation before and after bilateral injection of the GABA-receptor agonist isoguvacine (50-70 nl, 10 mM) into the KFn (n = 11). Our results show that bilateral inhibition of the KFn triggers apneusis (prolonged inspiration) and abolished pre-inspiratory discharge of facial, vagal and hypoglossal nerves as well as post-inspiratory discharge in the vagus. We conclude that the KFn plays a critical role for the eupneic regulation of naso-pharyngeal airway patency and the potential functions of the KFn in regulating airway patency and orofacial behavior is discussed., (Copyright © 2020. Published by Elsevier B.V.)

Objective: The aim of this study was to investigate the effects of systemic administration of decorin (DC) on facial nerve (FN) regeneration., Methods: A total of 32 female albino Wistar rats were divided into 4 groups: control (C) group: no bilateral FN neurorrhaphy (B-FNN), no DC application, sham-operated group: B-FNN without DC application, DC group: DC application without B-FNN, and B-FNN + DC group: B-FNN and DC application. Nerve conduction studies were performed before and after skin incisions at 1st, 3rd, 5th, and 7th weeks in all groups. The amplitude and latency of compound muscle action potentials were recorded. FN samples were obtained and were investigated under light microscopy and immunohistochemical staining. The nerve and axon diameter, number of axons, H score, Schwann cell proliferation, and myelin and axonal degeneration were recorded quantitatively., Results: In the sham group, the 3rd and 5th postoperative week, amplitude values were significantly lower than those of the B-FNN + DC group (p < 0.05). Nerve diameters were found to be significantly larger in the sham, DC, and B-FNN + DC groups than in the C group (p < 0.05). The number of axons, the axon diameter, and the H scores were found to be significantly higher in the B-FNN + DC group than in the sham group (p < 0.05). The Schwann cell proliferation, myelin degeneration, and axonal degeneration scores were significantly lower in the B-FNN + DC group than in the sham group (p < 0.05)., Conclusion: Electrophysiological and histopathological evaluation revealed the potential benefits provided by DC. This agent may increase FN regeneration., (© 2021 S. Karger AG, Basel.)

Bell's Palsy is the most frequent acute neuropathy of cranial nerves; it has been associated in various reports to herpes viruses. In a prospective study we searched the presence of DNA from five herpes viruses (HSV-1 and 2, VZV, EBV and HHV-6) in 79 patients at the acute phase of Bell's Palsy. Results were related with various parameters; age, gender and clinical outcome. We found the significant presence (p˂0.001) of HSV-1 and VZV in 39% and 42% of patients. However, a large percentage of cases were negative. When comparisons were made between subgroups according to gender and age no differences were found with viral findings nor with clinical outcome of palsy, which was of clinical remission in most cases (78%). Our results suggest that herpes viruses might participate in the complex mechanisms of autoimmunity of Bell's Palsy but not as determinant etiological element., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The efficacy of insulin-like growth factor 1 (IGF-1) in the treatment of peripheral facial nerve palsy was investigated using an animal model. The facial nerve within the temporal bone was exposed and compressed by clamping. The animals were treated with either IGF-1 or saline which was topically administered by a gelatin-based sustained-release hydrogel via an intratemporal route. The recovery from facial nerve palsy was evaluated at 8 weeks postoperatively based on eyelid closure, complete recovery rate, electroneurography and number of axons found on the facial nerve. IGF-1 treatment resulted in significant improvement in the changes of the degree of eyelid closure over the total time period and complete recovery rate. A separate study showed that IGF-1 receptor mRNA was expressed in facial nerves up to 14 days after the nerve-clamping procedure. IGF-1 was thus found to be effective in the treatment of peripheral facial nerve palsy when topically applied using a sustained-release gelatin-based hydrogel via an intratemporal route.

Facial nerves are frequently crushed or cut during facial surgery. In this study, the feasibility of repairing facial nerves in rabbits after crush or cut off injury was evaluated using collagen conduits with A collagen-binding domain (CBD)-human basic fibroblast growth factor (bFGF). A total of 39 six-month-old New Zealand White rabbits were randomly divided into four groups of nine rabbits, and bilateral crush or cut off injuries were made on each animal's face. Three rabbits were classified as the healthy control. The facial nerves were cut or crushed and then were either untreated or wrapped with a collagen conduit plus bFGF. At the 15, 30, and 90 days after the injury, three rabbits in each group were sacrificed. Regeneration of the injured facial nerve was evaluated using electrophysiological examination (compound muscle action potentials, CAMPs), scanning electron microscopy, and histological observation. The results suggested that using collagen conduits with recombinant proteins CBD-bFGF to repair facial nerves with crush or cut off injuries promoted functional facial nerve recovery. This treatment, as a possible therapeutic for patients with facial nerve injury, requires further investigation., (© 2020 Wiley Periodicals, Inc.)

Background: Local anesthetic toxicity has been well-documented to cause neuronal injury, death, and dysfunction, particularly in a susceptible nerve., Objective: To determine whether select local anesthetics affect neuron survival and/or functional recovery of an injured nerve., Methods: This report describes 6 separate experiments that test immediate or delayed application of local anesthetics in 3 nerve injury models. Adult C57/black6 male mice underwent a facial nerve sham, transection, or crush injury. Local anesthetic or saline was applied to the facial nerve at the time of injury (immediate) or 1 day after injury (delayed). Average percent facial motoneuron (FMN) survival was evaluated four-weeks after injury. Facial nerve regeneration was estimated by observing functional recovery of eye blink reflex and vibrissae movement after facial nerve crush injury., Results: FMN survival after: transection + immediate treatment with ropivacaine (54.8%), bupivacaine (63.2%), or tetracaine (66.9%) was lower than saline (85.5%) and liposomal bupivacaine (85.0%); crush + immediate treatment with bupivacaine (92.8%) was lower than saline (100.7%) and liposomal bupivacaine (99.3%); sham + delayed treatment with bupivacaine (89.9%) was lower than saline (96.6%) and lidocaine (99.5%); transection + delayed treatment with bupivacaine (67.3%) was lower than saline (78.4%) and liposomal bupivacaine (77.6%); crush + delayed treatment with bupivacaine (85.3%) was lower than saline (97.9%) and lidocaine (96.0%). The average post-operative time for mice to fully recover after: crush + immediate treatment with bupivacaine (12.83 days) was longer than saline (11.08 days) and lidocaine (10.92 days); crush + delayed treatment with bupivacaine (16.79 days) was longer than saline (12.73 days) and lidocaine (11.14 days)., Conclusions: Our data demonstrate that some local anesthetics, but not all, exacerbate motoneuron death and delay functional recovery after a peripheral nerve injury. These and future results may lead to clinical strategies that decrease the risk of neural deficit following peripheral nerve blocks with local anesthetics.

Several case studies have suggested the usefulness of peripheral nerve blocks in the management of various types of chronic pain that are unresponsive to standard medical treatment. We report here the case of a patient with severe neuralgia, secondary to Ramsay Hunt syndrome that was refractory to standard drug therapy. As a last resort, a block of the terminal branches of nervus intermedius was performed. Despite transient facial paralysis, pain was markedly reduced for 3 months with self-reported improved quality of life. To our knowledge, this block has never been described previously.

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.

Purpose: This study analyzes the effect of oxaliplatin treatment on the facial nerve. The facial nerve is the most commonly paralyzed cranial motor nerve because it advances through a long, curved bone canal. Electroneurography and blink reflex are the electrophysiological measurements used for evaluating facial nerve function. Oxaliplatin is a cytotoxic agent used in adjuvant or palliative systemic therapy for colorectal cancer treatment., Methods: This study was performed on 20 individuals who were at least 18 years old at Hacettepe University Ear Nose Throat Department, Audiology and Speech Disorders Unit, and Neurology Division EMG Laboratory as they received oxaliplatin treatment from Hacettepe University Oncology Hospital. Electroneurography and blink-reflex values were recorded and examined. The parameters taken during the second and fourth months were compared for this purpose., Results: This study shows that the prolongation of distal latencies of compound muscle action potential is statistically significant, the amplitudes showed no difference. The ENoG results were analyzed, the prolongation of latency measurements between pre-treatment and the fourth month after treatment were statistically significant. The blink-reflex results showed that comparison with the baseline values, the prolongation of latencies in R1 measurements between pre-treatment, the second month, and the fourth month were significant., Conclusions: The facial nerve is affected asymptomatically by oxaliplatin treatment. During oxaliplatin treatment, the evaluation of facial nerve function could be beneficial for patients by improving their quality of life. Electroneurography and blink-reflex tests can be used in the early evaluations of different medicines to determine their neurotoxicity.

Objectives: To investigate the effects of topical and systemic administrations of melatonin and dexamethasone on facial nerve regeneration., Materials and Methods: In total, 50 male albino Wistar rats underwent facial nerve axotomy and neurorrhaphy. The animals were divided into 5 groups: control, topical melatonin, systemic melatonin, topical dexamethasone, and systemic dexamethasone. Nerve conduction studies were performed preoperatively and at 3, 6, 9, and 12 weeks after drug administrations. Amplitude and latency of the compound muscle action potentials were recorded. Coapted facial nerves were investigated under light and electron microscopy. Nerve diameter, axon diameter, and myelin thickness were recorded quantitatively., Results: Amplitudes decreased and latencies increased in both the melatonin and dexamethasone groups. At the final examination, the electrophysiological evidence of facial nerve degeneration was not significantly different between the groups. Histopathological examinations revealed the largest nerve diameter in the melatonin groups, followed by the dexamethasone and control groups (p<0.05). Axon diameter of the control group was smaller than those of the melatonin (topical and systemic) and topical dexamethasone groups (p<0.05). The melatonin groups had almost normal myelin ultrastructure., Conclusion: Electrophysiological evaluation did not reveal any potential benefit of dexamethasone and melatonin in contrast to histopathological examination, which revealed beneficial effects of melatonin in particular. These agents may increase the regeneration of facial nerves, but electrophysiological evidence of regeneration may appear later.

Facial nerve injury is a clinically common disease accompanied by demyelination of damaged nerves. The remyelination of damaged nerves and the unsatisfactory function recovery are problems that have been plaguing people for a long time. The role that CXCL12 plays after facial nerve injury remains unknown. Our experiments found that the expression of CXCL12 was up-regulated in the early stage of facial nerve injury and decreased after two weeks. Further research found that CXCL12 had no effect on Schwann cells proliferation, apoptosis and cell cycle, while significantly promoted Schwann cells migration. Treatment with CXCL12 decreased the phosphorylation of PI3K, AKT and mTOR, but increased autophagy marker LC3II/I. The CXCL12-induced Schwann cells migration was significantly attenuated by inhibition of autophagy and activation of PI3K pathway through pretreatment with 3-MA and IGF-1 respectively, and this effect was enhanced by PI3K pathway inhibitor LY294002. Animal experiment also confirmed that CXCL12 could improve facial nerve function and myelin regeneration. The findings of this study indicate that CXCL12 can promote the migration of Schwann cells and potentially become a key molecule in the repair of facial nerve injury., (Copyright © 2018. Published by Elsevier B.V.)

Olfactory mucosa contains neural stem cells, called olfactory stem cells (OSCs), which produce trophic support required for promoting axonal regeneration after nerve injury. However, the local tissue environment can reduce the viability/function of transplanted cells when placed directly on the injury. Although gelatin hydrogels have been shown to aid cell survival during transplantation, such OSC-hydrogel combinations have not been extensively tested, particularly during recovery from facial nerve palsy. In this study, OSCs were isolated from the olfactory mucosae of newborn mice and were shown to express neural stem cell markers before differentiation, as well as cell-type specific markers after differentiation, confirming their multipotency. The OSCs also secrete growth factors and various cytokines that promote nerve regeneration. To test the effects of OSC transplantation in vivo, Medgel, a biodegradable hydrogel sponge, was applied to retain OSCs around the injury site and to lessen the detrimental effects of the local environment in an established facial nerve palsy mouse model. When OSCs were transplanted into the injury site, accelerated recovery was observed for 1 week. When OSCs were transplanted with Medgel, a higher level and duration of accelerated recovery was observed. OSCs in Medgel also increased peripheral nerve function and increased the number of regenerated nerve fibers. These results suggest that OSCs implanted with Medgel accelerate and enhance recovery from facial palsy in mice. Because human OSCs can be easily obtained from olfactory mucosa biopsies with limited risk, this OSC-Medgel combination is a candidate treatment option for accelerating recovery after facial nerve injury. Stem Cells Translational Medicine 2019;8:169&10., (© 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Background and Objectives: Ultrasound-guided intermediate cervical plexus block with perivascular local anesthetic infiltration is an established anesthetic procedure for carotid endarterectomy. In this prospective pilot study an additional subplatysmal block of the superficial ansa cervicalis is presented for the first time. The target structures are the anastomoses between the facial nerve (cervical and marginal mandibular branches) and cervical plexus., Methods: An ultrasound-guided intermediate cervical plexus block (20 ml of ropivacaine 0.75%) was performed (n = 28). Then, depending on the individual sonoanatomy, 5 ml of prilocaine 1% was injected into the carotid sheath (group 1: no perivascular infiltration, n = 14, group 2: perivascular infiltration, n = 14). The third step was subplatysmal injection of 5 ml of prilocaine 1% between the medial edge of the sternocleidomastoid muscle and the submandibular gland (n = 28). The investigated parameters included the need for supplementation and block-related side effects., Results: The requirement for supplemental local anesthetic infiltration in the skin incision area was minimal at mean (M) 1.1 ml (standard deviation (SD) ±2.4 ml). Perivascular infiltration in group 2 significantly decreased the total amount of local anesthetic supplemented: group 1 M = 4.2 ml (SD = ±3.1 ml), group 2 M = 1.7 ml (SD = ±2.0 ml) (p = 0.018). The incidence of block-related side effects was not significantly different between the two groups., Conclusion: This study presents an ultrasound-guided subplatysmal block of the superficial ansa cervicalis for the first time, with the aim of optimizing anesthesia quality during surgical interventions in the carotid triangle.

Acute facial paralysis (FP) describes acute onset of partial or complete weakness of the facial muscles innervated by the facial nerve. Acute FP occurs within a few hours to days. The differential diagnosis is broad; however, the most common cause is viral-associated Bell Palsy. A comprehensive history and physical examination are essential in arriving at a diagnosis. Medical treatment for acute FP depends on the specific diagnosis; however, corticosteroids and antiviral medications are the cornerstone of therapy. Lack of recovery after 4 months should prompt further diagnostic workup., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to investigate the long-term effect and treatment stability of selective neurectomy for refractory periocular synkinesis., Methods: We performed a retrospective review of all patients treated with highly selective neurectomy for refractory periocular synkinesis between August 2009 and August 2015. Primary outcome was time to recommencing treatment for periocular synkinesis. Palpebral fissure width was measured preoperatively, postoperatively, and at long-term ( > 2.5 years) follow-up. Mean units of botulinum toxin used pre- and postoperatively were compared., Results: Of the 12 patients, 10 could be included. Only one was free of treatment for periocular synkinesis at a follow-up of 3.5 years. The other nine patients recommenced treatment with botulinum toxin after a median time of 1.2 (interquartile range 0.6-2.6) years. Palpebral fissure width while smiling was significantly different between the pre- and postoperative (P = 0.008) and preoperative and long-term (P = 0.008) measurements. Postoperatively, previously refractory patients demonstrated good response to botulinum toxin treatments., Conclusion: This study demonstrates that most patients require renewed pharmacological treatment of periocular synkinesis after neurectomy. Although the effect of neurectomy in the treatment of refractory synkinesis does not appear to be sustained, patients usually experience a symptom-free interval and demonstrate larger palpebral fissure width at long-term follow-up compared to preoperative measurements., Level of Evidence: 4. Laryngoscope, 128:2291-2295, 2018., (© 2018 The Authors The Laryngoscope published by Wiley Periodicals, Inc. on behalf of American Laryngological, Rhinological and Otological Society Inc, “The Triological Society” and American Laryngological Association (ALA).)

Objective: Sodium-2-mercaptoethanesulfonate (MESNA) is widely used in medicine because of its antioxidant and mucolytic effects. In recent years, it has been used in otologic surgery. Because it cleaves disulfide bonds, it is used to easily dissect the epithelial matrix in cholesteatoma and atelectasis. In this study, we hypothesized that MESNA does not have any toxic effect on the facial nerve, and the effects of MESNA on the facial nerve were examined histologically and electrophysiologically., Materials and Methods: Twenty Wistar albino rats were used. Groups A and B were designated as the control and sham groups, respectively. The animals in groups C and D were administered 20% and 50% of MESNA solution, respectively, after the facial nerve was exposed in the parotid region. Electromyography (EMG) measurements were performed preoperatively and postoperatively at 4 weeks. The animals were subsequently euthanized; facial nerve samples were taken for histopathological examination., Results: When EMG parameters were compared within and between each group, preoperative and postoperative results were not statistically significantly different. Histopathological examination showed that MESNA did not cause any inflammation, granulation tissue, or foreign body reaction., Conclusion: To the best of our knowledge, the effects of MESNA on facial nerve functions have not been investigated. In this study, the effects of MESNA after direct application to the facial nerve were examined electrophysiologically and histologically, and it was determined that MESNA did not cause any toxic effects. It was concluded that MESNA can, therefore, be safely used during middle ear surgery.

Non-genetic induction of somatic cells into neural crest stem-like cells (NCSCs) is promising for potential cell-based therapies for post-traumatic peripheral nerve regeneration. Here, we report that human gingiva-derived mesenchymal stem cells (GMSCs) could be reproducibly and readily induced into NCSCs via non-genetic approaches. Compared to parental GMSCs, induced NCSC population had increased expression in NCSC-related genes and displayed robust differentiation into neuronal and Schwann-like cells. Knockdown of the expression of Yes-associated protein 1 (YAP1), a critical mechanosensor and mechanotransducer, attenuated the expression of NCSC-related genes; specific blocking of RhoA/ROCK activity and non-muscle myosin II (NM II)-dependent contraction suppressed YAP1 and NCSC-related genes and concurrently abolished neural spheroid formation in NCSCs. Using a rat model of facial nerve defect, implantation of NCSC-laden nerve conduits promoted functional regeneration of the injured nerve. These promising findings demonstrate that induced NCSCs derived from GMSCs represent an easily accessible and promising source of neural stem-like cells for peripheral nerve regeneration.

Facial nerve injury can cause severe long-term physical and psychological morbidity. There are limited repair options for an acutely transected facial nerve not amenable to primary neurorrhaphy. We hypothesize that a peptide amphiphile nanofiber neurograft may provide the nanostructure necessary to guide organized neural regeneration. Five experimental groups were compared, animals with (1) an intact nerve, (2) following resection of a nerve segment, and following resection and immediate repair with either a (3) autograft (using the resected nerve segment), (4) neurograft, or (5) empty conduit. The buccal branch of the rat facial nerve was directly stimulated with charge balanced biphasic electrical current pulses at different current amplitudes whereas nerve compound action potentials (nCAPs) and electromygraphic responses were recorded. After 8 weeks, the proximal buccal branch was surgically reexposed and electrically evoked nCAPs were recorded for groups 1-5. As expected, the intact nerves required significantly lower current amplitudes to evoke an nCAP than those repaired with the neurograft and autograft nerves. For other electrophysiologic parameters such as latency and maximum nCAP, there was no significant difference between the intact, autograft, and neurograft groups. The resected group had variable responses to electrical stimulation, and the empty tube group was electrically silent. Immunohistochemical analysis and transmission electron microscopy confirmed myelinated neural regeneration. This study demonstrates that the neuroregenerative capability of peptide amphiphile nanofiber neurografts is similar to the current clinical gold standard method of repair and holds potential as an off-the-shelf solution for facial reanimation and potentially peripheral nerve repair., (Copyright © 2018 John Wiley & Sons, Ltd.)

Objective: MESNA (Sodium-2-mercaptoethanesulfonate) is a mucolytic substance that is used for chemically assisted tissue dissection in various surgical operations. The aim of this study was to address the issue of possible neurotoxicity from topical administration of MESNA solution on the facial nerve. We used different concentrations of MESNA solution and evaluated their effects on facial nerve by histopathological and functional analysis., Materials and Methods: These groups were the saline administered group (control) (3 rats, 6 facial nerves), the 25% MESNA solution group (3 rats, 6 facial nerves), and the 100% MESNA solution group (3 rats, 6 facial nerves). Under general anesthesia (ketamine 150 mg/kg, xylocaine 4 mg/kg), the bilateral facial nerves of rats were dissected. The saline, 25% MESNA, and 100% MESNA solutions. Facial nerve functions of the rats were evaluated using mustachewhisker and blink reflex scores at day 20 days. On day 20, the rats were sacrificed and the buccal and marginal mandibular branches of the facial nerve were removed. The specimens were examined in terms of inflammation, granulation tissue, and foreign body reaction formation around the nerve. The functional and histopathological changes on facial nerves were compared between groups., Results: Mustache and blink reflex scores of the rats were 5 (normal) in both the control and study groups. There were no statistically significant differences between the three groups in terms of facial nerve functions (p=1.00). On histopathologic examination, the 25% and 100% MESNA groups had significantly more inflammation compared with the control group (p=0.038 and p=0.007, respectively). There were no statistically significant differences between the 25% and 100% MESNA groups in term of inflammation (p > 0.05). There were no statistically significant differences between the three groups in terms of foreign body reaction formation (p > 0.05)., Conclusion: Topical administration of MESNA solution onto the facial nerve causes increased inflammation in both the 25% and 100% concentrations. Nevertheless, it does not cause any facial nerve dysfunction.

Objective: We sought to validate the feasibility of facial motor evoked potential (FMEP) in facial nerve (FN) monitoring during vestibular schwannoma (VS) surgery under 2 anesthesia protocols and to examine its value for postoperative prognosis., Methods: This prospective study included 106 patients with VS who underwent microsurgical excision between May 2014 and November 2016 at the Beijing Tiantan Hospital, Capital Medical University, China. All patients were investigated for FMEP elicited by transcranial electrical stimulation in the contralateral facial motor cortex. The patients randomly received total intravenous anesthesia or combined intravenous-inhalation anesthesia. Postoperative FN function was evaluated 7-10 days after surgery (short-term) and at the last follow-up (long-term) using the House-Brackmann (HB) grading system. HB grades 1 and 2 were deemed satisfactory, whereas HB grades 3-6 were deemed unsatisfactory. The value of the final-to-start FMEP ratio for predicting short-term and long-term postoperative FN functions was examined., Results: Valid FMEPs were obtained in 97 patients, which were recorded from the mentalis muscle. The FMEP amplitude ratio was significantly correlated with short-term and long-term postoperative FN functions. Receiver operating characteristic curve analysis showed that the FMEP ratio cut-off values of 77.4% (area under the curve = 0.797) and 56.9% (area under the curve = 0.900) predicted satisfactory FN function 7-10 days after surgery and at the last follow-up, respectively. No statistically significant difference was found in FMEP quantitative parameters between the 2 anesthesia protocols., Conclusion: The FMEP amplitude ratio is a valuable predictor for postoperative FN function. FMEP ratio ≥57% is predictive of satisfactory long-term FN function., (Copyright © 2017. Published by Elsevier Inc.)

Background: Cat scratch disease is a common infectious disorder caused by Bartonella henselae that is transmitted primarily by kittens. It typically exhibits a benign and self-limiting course of subacute regional lymphadenopathy and fever lasting two to eight weeks. The most severe complication of cat scratch disease is involvement of the nervous system, such as encephalitis, meningitis, and polyneuritis. Peripheral facial nerve palsy associated with Bartonella infection is rare; few reported pediatric and adult cases exist and the precise pathogenesis is unknown., Case Report: A previously healthy 7-year-old boy presented with fever, cervical lymphadenopathy, and peripheral facial nerve palsy associated with serologically confirmed cat scratch disease. The stapedius muscle reflex was absent on the left side and brain magnetic resonance imaging revealed a mass lesion at the left internal auditory meatus. The patient's symptoms and imaging findings were gradually resolved after the antibiotics and corticosteroids treatment., Conclusions: The suspected granulomatous lesion was considered to have resulted from the host's immune reaction to Bartonella infection and impaired the facial nerve. This is the first case report providing direct evidence of peripheral facial nerve palsy caused by a suspected granulomatous lesion associated with cat scratch disease and its treatment course., (Copyright © 2017. Published by Elsevier B.V.)

It is well-known that, after nerve transection and surgical repair, misdirected regrowth of regenerating motor axons may occur in three ways. The first way is that the axons enter into endoneurial tubes that they did not previously occupy, regenerate through incorrect fascicles and reinnervate muscles that they did not formerly supply. Consequently the activation of these muscles results in inappropriate movements. The second way is that, in contrast with the precise target-directed pathfinding by elongating motor nerves during embryonic development, several axons rather than a single axon grow out from each transected nerve fiber. The third way of misdirection occurs by the intramuscular terminal branching (sprouting) of each regenerating axon to culminate in some polyinnervation of neuromuscular junctions, i.e. reinnervation of junctions by more than a single axon. Presently, "fascicular" or "topographic specificity" cannot be achieved and hence target-directed nerve regeneration is, as yet, unattainable. Nonetheless, motor and sensory reinnervation of appropriate endoneurial tubes does occur and can be promoted by brief nerve electrical stimulation. This review considers the expression of neurotrophic factors in the neuromuscular system and how this expression can promote functional recovery, with emphasis on the whisking of vibrissae on the rat face in relationship to the expression of the factors. Evidence is reviewed for a role of neurotrophic factors as short-range diffusible sprouting stimuli in promoting complete functional recovery of vibrissal whisking in blind Sprague Dawley (SD)/RCS rats but not in SD rats with normal vision, after facial nerve transection and surgical repair. Briefly, a complicated time course of growth factor expression in the nerves and denervated muscles include (1) an early increase in FGF2 and IGF2, (2) reduced NGF between 2 and 14days after nerve transection and surgical repair, (3) a late rise in BDNF and (4) reduced IGF1 protein in the denervated muscles at 28days. These findings suggest that recovery of motor function after peripheral nerve injury is due, at least in part, to a complex regulation of nerve injury-associated neurotrophic factors and cytokines at the neuromuscular junctions of denervated muscles. In particular, the increase of FGF2 and concomittant decrease of NGF during the first week after facial nerve-nerve anastomosis in SD/RCS blind rats may prevent intramuscular axon sprouting and, in turn, reduce poly-innervation of the neuromuscular junction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) presents uncommonly with cranial nerve involvement with ophthalmological implications., Methods: We report the case of a 37year-old man who developed CIDP which manifested as progressive and relapsing bilateral facial nerve palsy with lagophthalmos and exposure keratopathy, in the setting of treatment of Crohn's disease with the anti-TNF-alpha agent adalimumab., Results: Symptoms gradually improved over the course of several months following withdrawal of adalimumab and treatment with intravenous immunoglobulin (IVIg) and oral prednisolone., Conclusion: Bilateral facial nerve involvement occurs uncommonly as a feature of CIDP in its classic form. The prognosis is good for recovery of facial nerve function with discontinuation of anti-TNF-alpha therapy and concurrent use of steroid and intravenous immunoglobulin in this case., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The use of neuromuscular blocking agent (NMBA) during anesthesia may interfere with facial nerve monitoring (FNM) during parotid surgery. Sugammadex has been reported to be an effective and safe reversal of rocuronium-induced neuromuscular block (NMB) during surgery. This study investigated the feasibility and clinical effectiveness of sugammadex for NMB reversal during FNM in Parotid surgery. Fifty patients undergoing parotid surgery were randomized allocated into conventional anesthesia group (Group C, n = 25) and sugammadex group (Group S, n = 25). Group C did not receive any NMBA. Group S received rocuronium 0.6 mg/kg at anesthesia induction and sugammadex 2 mg/kg at skin incision. The intubating condition and influence on FNM evoked EMG results were compared between groups. The intubation condition showed significantly better in group S patients than C group patients (excellent in 96% v.s. 24%). In group S, rapid reverse of NMB was found and the twitch (%) recovered from 0 to >90% within 10 min. Positive and high EMG signals were obtained in all patients at the time point of initial facial nerve stimulation in both groups. There was no significant difference as comparing the EMG amplitudes detected at the time point of initial and final facial nerve stimulation in both groups. Implementation of sugammadex in anesthesia protocol is feasible and reliable for successful FNM during parotid surgery., (Copyright © 2017. Published by Elsevier Taiwan.)

Previous research has indicated that differences in sensitivities to muscle relaxants exist between facial nerve- and somatic nerve-innervated muscles. Here, we report that the 50% inhibitory concentration (IC50) values for rocuronium were significantly larger in the normal orbicularis oris than those in the gastrocnemius. Increased IC50 values and reduced twitch tension were observed after facial nerve injury. The normal orbicularis oris had a smaller muscle fiber cross-sectional area (CSA) and a larger ratio of endplate surface area (ESA) to muscle fiber CSA (ESA/CSA), but no difference was found in the density of nicotinic acetylcholine receptor (nAChR) subunits on endplates between normal orbicularis oris and gastrocnemius. Expression of the nAChR α1, β1, δ, ε, and γ subunits increased significantly on the postsynaptic membranes of endplates and extra-junctional muscle membranes after facial nerve injury. Our results suggest that facial nerve-innervated muscle was less sensitive than somatic nerve-innervated muscle, and the mechanisms underlying this result may be related to muscle fiber CSA and the ESA/CSA ratio, but not to the density of nAChR subunits on endplates. Facial nerve injury caused the resistance to neuromuscular blockers and reduced twitch tension, which was related to qualitative, quantitative, and locational changes in nAChR subunits.

Objective: To evaluate the effect of agmatine sulphate on facial nerve regeneration after facial nerve injury using electron and light microscopy., Methods: The study was performed on 30 male Wistar albino rats split into: a control group, a sham-treated group, a study control group, an anastomosis group, and an anastomosis plus agmatine sulphate treatment group. The mandibular branch of the facial nerve was dissected, and a piece was removed for histological and electron microscopic examination., Results: Regeneration was better in the anastomosis group than in the study control group. However, the best regeneration findings were seen in the agmatine sulphate treatment group. There was a significant difference between the agmatine group and the others in terms of median axon numbers (p < 0.004) and diameters (p < 0.004)., Conclusion: Agmatine sulphate treatment with anastomosis in traumatic facial paralysis may enhance nerve regeneration.

Traumatic facial nerve injury, an important cause of facial paralysis, has a number of adverse effects, including facial muscle dysfunction and facial asymmetry. It has been demonstrated in our previous work that native human NT-3 fused with a collagen-binding domain (CBD-NT-3) could bind to collagen, specifically to exert neurotrophic effects, promoting axonal regeneration. To evaluate the effect of CBD-NT-3 in inducing facial nerve regeneration and functional recovery, the differing effects of CBD-NT-3 and native neurotrophin-3 (NAT-NT-3) were observed using the results of facial nerve functional recovery, electrophysiological testing, and axonal and myelin changes in a rat model of facial nerve crush injury. The rats were injected in the epineurium in crushed fibers of the facial nerve with CBD-NT-3, NAT-NT-3, and PBS respectively. After 4 weeks, the CBD-NT-3 group demonstrated significantly more ordered growth of axons and nerve functional recovery than the NAT-NT-3 group. The results suggest that CBD-NT-3 considerably enhances facial nerve regeneration and functional recovery., (© 2016 by the Association of Clinical Scientists, Inc.)

Fingolimod (FTY720) is a new generation oral treatment for multiple sclerosis (MS). So far, FTY720 was mainly considered to target trafficking of immune cells but not brain cells such as neurons. Herein, we analyzed FTY720's potential to directly alter neuronal function. In CNS neurons, we identified a FTY720 governed gene expression response. FTY720 upregulated immediate early genes (IEGs) encoding for neuronal activity associated transcription factors such as c-Fos, FosB, Egr1 and Egr2 and induced actin cytoskeleton associated genes (actin isoforms, tropomyosin, calponin). Stimulation of primary neurons with FTY720 enhanced neurite growth and altered growth cone morphology. In accordance, FTY720 enhanced axon regeneration in mice upon facial nerve axotomy. We identified components of a FTY720 engaged signaling cascade including S1P receptors, G12/13G-proteins, RhoA-GTPases and the transcription factors SRF/MRTF. In summary, we uncovered a broader cellular and therapeutic operation mode of FTY720, suggesting beneficial FTY720 effects also on CNS neurons during MS therapy and for treatment of other neurodegenerative diseases requiring neuroprotective and neurorestorative processes., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Objective: The effect of direct application of local lidocaine with epinephrine on the facial nerve (FN) has not been reported. The aim of this study is to assess the effects of 2% lidocaine with 1:100,000 epinephrine at clinically relevant concentrations in a rat FN model with respect to facial nerve blood flow (FNBF) and subsequent electrophysiological changes., Materials and Methods: To assess the influence of drugs on FNBF and electrically evoked muscle action potential (EMAP), small pieces of gelfoam were soaked in PBS 100μl (n=5, control group), 50μl (n=5, treatment group A) and 100μl (n=5, group B) of 2% lidocaine with 1:100,000 epinephrine, and 50μl (n=5, group C) and 100μl (n=5, group D) of 2% lidocaine. After 5min of stable recordings, we applied a 2% lidocaine with or without 1:100,000 epinephrine impregnated gelfoam over the main trunk of the facial nerve of rats for 30min. After removing the applied gelfoam, FNBF and threshold of EMAP were measured separately in each group., Results: Compared to the control group, the treatment groups showed a significant reduction in FNBF in a dose-dependent manner. The maximal reductions in FNBF were observed in all treatment groups for a period after 10min of the application. Synergistic reduction in FNBF was greater in groups A and B than in the lidocaine applied groups (C and D). The maximal increase in the EMAP threshold was observed immediately after the respective drug application in all groups. The greatest increase in the EMAP threshold was observed in group B. The increased EMAP threshold returned to the baseline value within 120min in groups A and C., Conclusion: From these results, it can be considered that the topical application of lidocaine with epinephrine caused reduction in FNBF and elevation of EMAP threshold. These acute reductions in FNBF and elevations in the EMAP threshold were restored in a time-dependent manner., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

To investigate the effect of FK506 on apoptosis of facial motor neurons in rats and its possible mechanism. A total of 48 Wistar rats were randomly divided into experimental group and control group. Facial nerve injury model was established by transection of facial nerve at stylomastoid foramen. Rats in experimental group and control group were provided with FK506 and normal saline by intraperitoneal injection, respectively. The morphology of facial neurons was observed under light microscope at different time points after injury. Apoptotic facial motor neurons were detected by TdT-mediated dUTP-biotin nick and labeling (TUNEL) staining, and expression of bcl-2 and bax was evaluated by immunohistochemistry. After facial nerve transection, the apoptotic cells in experimental group significantly decreased compared to control group (P < 0.05), with higher expression of bcl-2 and lower expression of bax in experimental group. FK506 could inhibit apoptosis of facial motor neurons after facial nerve transection, possibly via up-regulation of bcl-2 expression and down-regulation of bax expression.

Background and Aim: Neuregulin-1 is an essential axoglial signal required for peripheral nerve development, and evidence that neuregulin-1 is also required for effective nerve repair is growing. In this study, the effects of neuregulin-1-impregnated gelatin hydrogels on nerve regeneration and functional recovery after anastomosis of the facial nerve were investigated in a rat model of traumatic facial nerve paralysis., Materials and Methods: Twenty-four adult male rats underwent complete resection of the facial nerve trunk, followed by end-to-end anastomosis with epineural sutures. The animals were then randomly allocated to one of three treatment groups (eight rats/group): no additional intervention (Group I), single-shot injection of neuregulin-1 into the epineurium of the facial nerve at the suture sites (Group II), or implantation of a hydrogel impregnated with neuregulin-1 at the injury site (Group III). After surgery, mimetic muscle movements were evaluated weekly. Eight weeks after surgery, the mimetic muscles were injected with a neural tracer (1,10-dioctadecyl-3,3,30,30-tetramethylindocarbocyanin perchlorate, DiI). Retrograde-labeled neurons were counted in the facial nuclei, and facial nerve specimens were stained with toluidine blue for histological examination of axon density., Results: Group III exhibited significantly faster recovery of mimetic muscle function, a higher density of large-diameter axons (>5 μm) in the facial nerve, and greater numbers of retrogradely labeled neurons in the ipsilateral facial nucleus compared with Groups I and II., Conclusions: Continuous release of neuregulin-1 from impregnated gelatin hydrogels can accelerate facial nerve regeneration., (Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Many studies have demonstrated that ischemia could induce facial nerve (FN) injury. However, there is a lack of a suitable animal model for FN injury study and thus little knowledge is available about the precise mechanism for FN injury. The aims of this study were to establish a reliable FN injury model induced by blocking the petrosal artery and to investigate whether dysfunctional interaction between cyclophilin D (CypD) and mitochondrial permeability transition pore (MPTP) can mediate cell dysfunction in ischemic FN injury. The outcomes of ischemia-induced FN injury rat model were evaluated by behavioral assessment, histological observation, electrophysiology, and electron microscopy. Then the levels of CypD and protein that forms the MPTP were evaluated under the conditions with or without the treatment of Cyclosporin A (CsA), which has been found to disrupt MPTP through the binding of CypD. The blocking of petrosal artery caused significant facial palsy signs in the ischemia group but not in the sham group. Furthermore, ischemia can induce the dysfunction of facial nucleus neurons and destruction of the myelin sheath and increase the protein levels of CypD and MPTP protein compared with sham group. Interestingly, treatment with CsA significantly improved neurological function and reversed the ischemia-induced increase of CypD and MPTP proteins in ischemia group. These results demonstrated that blocking of petrosal artery in rats can induce FN injury and the mechanism may be related to the disruption of MPTP by CypD.

The Ranvier nodes of thick myelinated nerve fibers contain almost exclusively voltage-gated sodium channels (Navs), while the unmyelinated fibers have several receptors (e.g., cannabinoid, transient receptor potential vanilloid receptor 1), too. Therefore, a nerve which contains only motor fibers can be an appropriate in vivo model for selective influence of Navs. The goals were to evaluate the potency of local anesthetic drugs on such a nerve in vivo; furthermore, to investigate the effects of ligands with different structures (arachidonic acid, anandamide, capsaicin and nisoxetine) that were proved to inhibit Navs in vitro with antinociceptive properties. The marginal mandibular branch of the facial nerve was explored in anesthetized Wistar rats; after its stimulation, the electrical activity of the vibrissae muscles was registered following the perineural injection of different drugs. Lidocaine, bupivacaine and ropivacaine evoked dose-dependent decrease in electromyographic activity, i.e., lidocaine had lower potency than bupivacaine or ropivacaine. QX-314 did not cause any effect by itself, but its co-application with lidocaine produced a prolonged inhibition. Nisoxetine had a very low potency. While anandamide and capsaicin in high doses caused about 50% decrease in the amplitude of action potential, arachidonic acid did not influence the responses. We proved that the classical local anesthetics have high potency on motor nerves, suggesting that this method might be a reliable model for selective targeting of Navs in vivo circumstances. It is proposed that the effects of these endogenous lipids and capsaicin on sensory fibers are not primarily mediated by Navs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: A signature EMG feature of hemifacial spasm (HFS) is the lateral spread response (LSR). Desflurane is a common anesthetic with potent effects on synaptic transmission. We tested the hypothesis that the LSR is mediated by corticobulbar components by comparing the LSR during total intravenous anesthesia (TIVA) or TIVA plus desflurane during microvascular decompression (MVD) surgery., Methods: 22 HFS patients undergoing MVD surgery participated in this prospective study. The LSR data was recorded from the o. oculi, o. oris and mentalis muscles prior to opening dura. LSR onset latencies and amplitudes were determined under TIVA and TIVA/desflurane (0.5 and 1MAC). Facial muscle LSRs and EEG were analyzed., Results: Desflurane (1MAC) significantly decreased the LSR amplitude in all 3 facial muscles (p<0.01). Pooled LSR data from all facial muscles showed desflurane inhibited the LSR amplitude by 43% compared to TIVA (p<0.001). No effects on the latency of the LSR or on EEG state were observed., Conclusions: LSR inhibition by desflurane suggests a central mechanism involvement in the genesis of this signature HFS response., Significance: This study demonstrates that facial nerve vascular compression and plastic changes within the CNS are part of the pathophysiology of HFS., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)