[Diagnosis and treatment of 68 cases of traumatic facial nerve paralysis].

Objective:To summarize the clinical characteristics and therapeutic effect of traumatic facial nerve palsy. Methods:Sixty-eight cases of traumatic facial nerve palsy were retrospectively analyzed from January 2015 to May 2023. Results:The median course of disease was 33 days. The facial nerve function of the patients was grade HB-Ⅱin 2 cases, grade HB-Ⅲ in 4 cases, grade HB-Ⅳin 16 cases, grade HB-Ⅴ in 37 cases（38 ears）, and grade HB-Ⅵ in 9 cases. 42 cases occurred immediately after injury and 26 cases were delayed. CT examination of temporal bone revealed longitudinal fractures in 51 cases（52 ears） , transverse fractures in 6 cases and mixed fractures in 4 cases. No definite temporal bone fracture was found in the remaining 7 cases. The segments of facial nerve injury in 49 cases（50 ears） were geniculate ganglion and adjacent, in 7 cases were vertical segment, in 7 cases were horizontal segment, in 2 cases were horizontal segment and vertical segment; and the other 3 cases could not be evaluated. Conservative treatment with glucocorticoids was used in 23 ears and surgery was used in 46 ears. Patients were followed up 6-24 months after treatment, including 20 cases of grade HB-Ⅰ, 19 cases of grade HB-Ⅱ, 23 cases（24 ears） of grade HB-Ⅲ, 4 cases of grade HB-Ⅳ, and 1 case of grade HB-Ⅴ.One patient was lost to follow-up. After treatment, the facial nerve function of patients was significantly improved（P<0.05）, and there were significant differences between conservative treatment group and surgical treatment group in the course of facial nerve palsy, the ratio of facial palsy immediately after injury, the nerve function before treatment and the nerve function after treatment（P<0.05）. There were no significant differences in age, sex, hearing condition, temporal bone fracture, facial nerve injury segment and rate of favorable neurologic outcomes（P>0.05）. The comparison of patients with neurodegeneration rate>90% and ≤90% showed that the facial nerve function of patients with neurodegeneration rate>90% before treatment was significantly worse（P<0.05）, but there was no significant difference between the facial nerve function after treatment（P>0.05）. There was no significant difference in facial nerve function between middle fossa approach group and mastoid approach group（P>0.05）. Conclusion:Patients with traumatic facial nerve palsy should be evaluated individually. Patients with mild facial nerve palsy, low neurodegeneration rate and short course of disease can be treated conservatively and followed up closely. Patients with severe facial nerve palsy, high neurodegeneration rate and more than 6 weeks of disease can be actively considered surgery. Good prognosis can be obtained by correct evaluation and treatment.

A basement membrane extract-based three-dimensional culture system promotes the neuronal differentiation of cochlear Sox10-positive glial cells in vitro.

Spiral ganglion neurons (SGNs) in the mammalian cochleae are essential for the delivery of acoustic information, and damage to SGNs can lead to permanent sensorineural hearing loss as SGNs are not capable of regeneration. Cochlear glial cells (GCs) might be a potential source for SGN regeneration, but the neuronal differentiation ability of GCs is limited and its properties are not clear yet. Here, we characterized the cochlear Sox10-positive (Sox10+) GCs as a neural progenitor population and developed a basement membrane extract-based three-dimensional (BME-3D) culture system to promote its neuronal generation capacity in vitro. Firstly, the purified Sox10+ GCs, isolated from Sox10-creER/tdTomato mice via flow cytometry, were able to form neurospheres after being cultured in the traditional suspension culture system, while significantly more neurospheres were found and the expression of stem cell-related genes was upregulated in the BME-3D culture group. Next, the BME-3D culture system promoted the neuronal differentiation ability of Sox10+ GCs, as evidenced by the increased number, neurite outgrowth, area of growth cones, and synapse density as well as the promoted excitability of newly induced neurons. Notably, the BME-3D culture system also intensified the reinnervation of newly generated neurons with HCs and protected the neurospheres and derived-neurons against cisplatin-induced damage. Finally, transcriptome sequencing analysis was performed to identify the characteristics of the differentiated neurons. These findings suggest that the BME-3D culture system considerably promotes the proliferation capacity and neuronal differentiation efficiency of Sox10+ GCs in vitro, thus providing a possible strategy for the SGN regeneration study.

Foreign Body Granuloma Originating From the Lateral Process of Malleus: A Case Series of 19 Children.

OBJECTIVE: A special presentation of foreign body granuloma originating from the lateral process of the malleus (FBGLP) was noted in the absence of a history of foreign body entry into the external auditory canal (EAC). This study reported the clinical features, pathology, and prognosis of patients with FBGLP. DESIGN: Retrospective study. SETTING: Shandong Provincial ENT Hospital. PATIENTS: Nineteen pediatric patients (age, 1-10 yr) with FBGLP. INTERVENTIONS: Clinical data were collected from January 2018 to January 2022. MAIN OUTCOME MEASURES: Clinicopathologic characteristics of the patients were analyzed. RESULTS: All patients had an acute course, and were within 3 months of ineffective medical treatment. The most common symptoms were suppurative (57.9%) and hemorrhagic (42.1%) otorrhea. FBGLP imaging examinations demonstrated a soft mass blocking the EAC without bone destruction and occasionally concomitant effusion in the middle ear. The most common pathologic findings were foreign body granuloma (94.7%,18/19), granulation tissue (73.7%, 14/19), keratotic precipitate (73.7%, 14/19), calcium deposition (63.2%, 12/19), hair shafts (47.4%, 9/19), cholesterol crystals (5, 26.3%), and hemosiderin (15.8%, 3/19). Foreign body granuloma and granulation tissue showed higher expression levels of CD68 and cleaved caspase-3 than did the normal tympanic mucosa, whereas Ki-67 levels were similarly low in all tissues. The patients were followed up for 3 months to 4 years without recurrence. CONCLUSION: FBGLP is caused by endogenous foreign particles in the ear. We recommend the trans-external auditory meatus approach for FBGLP surgical excision, as this shows promising outcomes.

TIGAR Protects Cochlear Hair Cells against Teicoplanin-Induced Damage.

Teicoplanin is a glycopeptide antibiotic used to treat severe staphylococcal infections. It has been claimed that teicoplanin possesses ototoxic potential, although its toxic effects on cochlear hair cells (HCs) remain unknown. The TP53-induced glycolysis and apoptosis regulator (TIGAR) plays a crucial role in promoting cell survival. Prior research has demonstrated that TIGAR protects spiral ganglion neurons against cisplatin damage. However, the significance of TIGAR in damage to mammalian HCs has not yet been investigated. In this study, firstly, we discovered that teicoplanin caused dose-dependent cell death in vitro in both HEI-OC1 cells and cochlear HCs. Next, we discovered that HCs and HEI-OC1 cells treated with teicoplanin exhibited a dramatically decrease in TIGAR expression. To investigate the involvement of TIGAR in inner ear injury caused by teicoplanin, the expression of TIGAR was either upregulated via recombinant adenovirus or downregulated by shRNA in HEI-OC1 cells. Overexpression of TIGAR increased cell viability, decreased apoptosis, and decreased intracellular reactive oxygen species (ROS) level, whereas downregulation of TIGAR decreased cell viability, exacerbated apoptosis, and elevated ROS level following teicoplanin injury. Finally, antioxidant therapy with N-acetyl-L-cysteine decreased ROS level, prevented cell death, and restored p38/phosphorylation-p38 expression levels in HEI-OC1 cells injured by teicoplanin. This study demonstrates that TIGAR may be a promising novel target for the prevention of teicoplanin-induced ototoxicity.

The Alterations and Significance of Intercellular Adhesion Molecule-1 in Mouse Brainstem During Herpes Simplex Virus Type 1-Induced Facial Palsy.

Herpes simplex virus type 1 (HSV-1) results in the development of Bell's pals but still, the pathophysiology of the facial nerve paralysis is still not fully studied. The main objective is to establish an animal model of type 1 herpes simplex virus (HSV-1)-induced face paralysis in the mouse and to investigate the pattern of changes in intercellular adhesion molecule -1(ICAM-1) expression in the facial nucleus of the brain stem in mice with facial paralysis as well as the effects of glucocorticoids on intercellular adhesion molecule -1(ICAM-1) expression. A total of 170 4-week-old Balb/c male mice were randomly divided into the virus inoculation group (n = 135), saline control group (n = 26), and blank control group (n = 9). Mice in the virus inoculation group that showed facial paralysis were divided into A, B, and C subgroups. The A group did not receive any treatments, the B group received methylprednisolone sodium succinate (MPSS) intervention, and the C group received MPSS + RU486 treatment. The mouse model of facial paralysis was established by inoculating HSV-1 to the skin at the back of the ears. The facial nerve function of mice was assessed, and real-time PCR and western blot were used to assess ICAM-1 expression in the facial nucleus of the brain stem in mice with facial paralysis after drug intervention. In the virus inoculation group, 95 mice (55.88%) showed varying degrees of facial paralysis symptoms within 2-5 days after inoculation. The ICAM-1 gene and protein expression levels remained at low levels in the facial nucleus of the brain stem of mice in the saline group, which showed no significant difference compared to the normal control group (P > 0.05). However, for mice of the virus inoculation group, ICAM-1 expression increased at 6 h after the occurrence of facial paralysis and peaked after 2 days, differing significantly from the blank control group (P < 0.01). ICAM-1 expression subsequently decreased gradually. In the HSV-1 + MPSS group, ICAM-1 protein expression decreased significantly on the 2nd day after facial paralysis. In the HSV-1 + MPSS + RU486 group, MPSS inhibition of ICAM-1 protein expression was reduced. The results suggested that ICAM-1 is involved in the pathological processes by which HSV-1 induces facial paralysis in mice, and the treatment effects of MPSS for Bell's palsy can be achieved by the inhibition of MCP-1.

Glutathione Peroxidase 1 Protects Against Peroxynitrite-Induced Spiral Ganglion Neuron Damage Through Attenuating NF-κB Pathway Activation.

Glutathione peroxidase 1 (GPX1) is a crucial antioxidant enzyme that prevented the harmful accumulation of intra-cellular hydrogen peroxide. GPX1 might contribute in limiting cochlear damages associated with aging or acoustic overexposure, but the function of GPX1 in the inner ear remains unclear. The present study was designed to investigate the effect of GPX1 on cochlear spiral ganglion neurons (SGNs) against oxidative stress induced by peroxynitrite, a versatile oxidant generated by the reaction of superoxide anion and nitric oxide. Here, we first found that the expression of GPX1 in cultured SGNs was downregulated after peroxynitrite exposure. Then, the GPX1 mimic ebselen and the gpx1 knockout (gpx1 -/-) mice were used to investigate the role of GPX1 in SGNs treated with peroxynitrite. The pretreatment with ebselen significantly increased the survived SGN numbers, inhibited the apoptosis, and enhanced the expression of 4-HNE in the cultured SGNs of peroxynitrite + ebselen group compared with the peroxynitrite-only group. On the contrary, remarkably less survived SGNs, more apoptotic SGNs, and the higher expression level of 4-HNE were detected in the peroxynitrite + gpx1 -/- group compared with the peroxynitrite-only group. Furthermore, rescue experiments with antioxidant N-acetylcysteine (NAC) showed that the expression of 4-HNE and the apoptosis in SGNs were significantly decreased, while the number of surviving SGNs was increased in peroxynitrite + NAC group compared the peroxynitrite-only group and in peroxynitrite + gpx1 -/- + NAC group vs. peroxynitrite + gpx1 -/- group. Finally, mechanistic studies showed that the activation of nuclear factor-kappa B (NF-κB) was involved in the SGNs damage caused by peroxynitrite and that GPX1 protected SGNs against peroxynitrite-induced damage, at least in part, via blocking the NF-κB pathway activation. Collectively, our findings suggest that GPX1 might serve as a new target for the prevention of nitrogen radical-induced SGNs damage and hearing loss.

c-Myb protects cochlear hair cells from cisplatin-induced damage via the PI3K/Akt signaling pathway.

The transcription factor c-Myb is vital for cell survival, proliferation, differentiation, and apoptosis. We have previously reported that c-Myb knockdown exacerbates neomycin-induced damage to cochlea cells. However, the function and regulation of c-Myb in the mammalian inner ear remains unclear. Here, we first found that the expression of c-Myb in cochlear HCs was downregulated after cisplatin damage in vivo. Next, to investigate the role of c-Myb in HCs treated with cisplatin, the recombinant virus AAV-ie-CAG-Myb-HA (AAV-c-Myb) that overexpresses c-Myb was constructed and transfected into HCs. The protein expression of c-Myb was effectively up-regulated in cultured cochlear HCs after the virus transfection, which increased cochlear HC viability, decreased HC apoptosis and reduced intracellular reactive oxygen species (ROS) levels after cisplatin injury in vitro. The overexpression of c-Myb in HCs after AAV-c-Myb transfection in vivo also promoted HC survival, improved the hearing function of mice and reduced HC apoptosis after cisplatin injury. Furthermore, c-Myb-HC conditional knockout mice (Prestin; c-Myb-cKO) in which c-Myb expression is downregulated only in cochlear OHCs were generated and the cisplatin-induced HCs loss, apoptosis and hearing deficit were all exacerbated in Prestin; c-Myb-cKO mice treated with cisplatin in vivo. Finally, mechanistic studies showed that upregulation of the PI3K/Akt signaling pathway by c-Myb contributed to the increased HC survival after cisplatin exposure in vitro. The findings from this work suggest that c-Myb might serve as a new target for the prevention of cisplatin-induced HC damage and hearing loss.

The effect of balloon dilatation eustachian tuboplasty combined with grommet insertion on the structure and function of the eustachian tube in patients with refractory otitis media with effusion.

BACKGROUND: The treatments for refractory secretory otitis media with effusion usually choose long-term grommet insertion. This study evaluated the effect of balloon eustachian tuboplasty combined with grommet insertion on the function and the opening length of the eustachian tube in patients with refractory otitis media with effusion. METHODS: Fifty-seven patients with refractory otitis media with effusion were enrolled. A three-dimensional reconstruction of an iohexol-enhanced computed tomography image was applied to evaluate the structural and length changes of the eustachian tube at both resting and Valsalva maneuver states. The grommet was removed 3 months after the operation and postoperative follow-up was carried out from 3 to 12 months. We performed pre- and post-operative observation of the following: appearance of the tympanic membrane, pure-tone audiometry threshold, eustachian tube score, seven-item Eustachian Tube Dysfunction Questionnaire scores (ETDQ-7), quantitative examination of eustachian tube function dynamic observation of tympanogram peak pressure point, and computed tomography examination of the eustachian tube. RESULTS: The pure-tone audiometry at 1, 3, 6, 9, and 12 months postoperatively were all significantly lower compared to the preoperative value (all P<0.05). There was no significant difference between the pure-tone audiometry at 6 and 9 months postoperatively, neither was for the air-bone conduction gap at these time points. The quantitative examination peak pressure deviation was markedly increased at 6 months postoperatively compared with that before the operation (all P<0.05). The peak pressure deviation of tympanometry at 6 and 9 months postoperatively were both higher than the value at 12 months after surgery (P<0.05). The eustachian tube score at 1, 3, 6, 9, and 12 months postoperatively were notably higher than that before the operation (all P<0.05). A significant difference was also observed between the 6- and 12-month postoperative eustachian tube score (P<0.05). There was a significant difference in the ETDQ-7 scores at 6- and 12-month postoperatively (P<0.05). The quantitative examination peak pressure deviation and eustachian tube score were both correlated with development length of the eustachian tube after three-dimensional computed tomography reconstruction (P<0.05). CONCLUSIONS: Eustachian tube balloon dilatation combined with grommet insertion is an effective treatment for refractory otitis media with effusion.

Extended high-frequency audiometry in healthy adults with different age groups.

BACKGROUND: It was well-documented that extended high-frequency (EHF, above 8 kHz) hearing test could be more sensitive comparing with the conventional measurement on frequency below 8 kHz, regarding the early prediction of auditory damage in certain population. However, hardly any age-specific thresholds of EHF in population with normal hearing ability were observed. This study aims to monitor the age-dependent hearing thresholds at EHF (from 9 to 20 kHz) in healthy hearing population. METHODS: A total of 162 healthy participants (from 21 to 70 years) with normal conventional pure tone audiograms were recruited and separated into five groups by age. Conventional pure tone average was performed with frequencies from 0.25 to 8 kHz under air conduction and from 0.25 to 4 kHz under bone conduction. EHF audiometry from 9 to 20 kHz was determined under air conduction. RESULTS: The effects of aging on hearing were evident at frequencies above 4 kHz. The hearing thresholds of EHF were less than 26 dB HL before 30 years-olds. Hearing abilities in EHF were deteriorated starting from the 31 ~ 40 group and were most obvious in the 51 ~ 60 group and the 61 ~ 70 group with the maximum thresholds of 75 dB HL. Sensitivity of EHF was inversely proportional to the frequency within each age group, and to age among groups. Subjects under 30 years old were totally responsive up to 16 kHz, and 52.2% could respond to 20 kHz. Meanwhile, no responsiveness was recorded to 20 kHz in the 51 ~ 60 group and even to 18 kHz in the 61 ~ 70 group. No gender differences in hearing threshold was observed within each age group, except an obvious decline at frequencies of 4, 6, 8, and 9 kHz in male participants of the 41 ~ 50 group. CONCLUSIONS: Hearing thresholds at EHF from 9 to 20 kHz were more sensitive than at frequencies below 8 kHz for hearing measurement, and aging inversely affected hearing ability at EHF in healthy population. Hearing thresholds at EHF deteriorated with age and raising frequency, while the upper frequency limit decreased with aging.

PRDX1 activates autophagy via the PTEN-AKT signaling pathway to protect against cisplatin-induced spiral ganglion neuron damage.

Spiral ganglion neurons (SGNs) are auditory neurons that relay sound signals from the inner ear to the brainstem. The ototoxic drug cisplatin can damage SGNs and thus lead to sensorineural hearing loss (SNHL), and there are currently no methods for preventing or treating this. Macroautophagy/autophagy plays a critical role in SGN development, but the effect of autophagy on cisplatin-induced SGN injury is unclear. Here, we first found that autophagic flux was activated in SGNs after cisplatin damage. The SGN apoptosis and related hearing loss induced by cisplatin were alleviated after co-treatment with the autophagy activator rapamycin, whereas these were exacerbated by the autophagy inhibitor 3-methyladenine, indicating that instead of inducing SGN death, autophagy played a neuroprotective role in SGNs treated with cisplatin both in vitro and in vivo. We further demonstrated that autophagy attenuated reactive oxygen species (ROS) accumulation and alleviated cisplatin-induced oxidative stress in SGNs to mediate its protective effects. Notably, the role of the antioxidant enzyme PRDX1 (peroxiredoxin 1) in modulating autophagy in SGNs was first identified. Deficiency in PRDX1 suppressed autophagy and increased SGN loss after cisplatin exposure, while upregulating PRDX1 pharmacologically or by adeno-associated virus activated autophagy and thus inhibited ROS accumulation and apoptosis and attenuated SGN loss induced by cisplatin. Finally, we showed that the underlying mechanism through which PRDX1 triggers autophagy in SGNs was, at least partially, through activation of the PTEN-AKT signaling pathway. These findings suggest potential therapeutic targets for the amelioration of drug-induced SNHL through autophagy activation.Abbreviations: 3-MA: 3-methyladenine; AAV : adeno-associated virus; ABR: auditory brainstem responses; AKT/protein kinase B: thymoma viral proto-oncogene; Baf: bafilomycin A1; CAP: compound action potential; COX4I1: cytochrome c oxidase subunit 4I1; Cys: cysteine; ER: endoplasmic reticulum; H2O2: hydrogen peroxide; HC: hair cell; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; NAC: N-acetylcysteine; PRDX1: peroxiredoxin 1; PTEN: phosphatase and tensin homolog; RAP: rapamycin; ROS: reactive oxygen species; SGNs: spiral ganglion neurons; SNHL: sensorineural hearing loss; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling; WT: wild type.

Characterization of EGR-1 Expression in the Auditory Cortex Following Kanamycin-Induced Hearing Loss in Mice.

Deprivation of acoustic input during a critical period leads to abnormal auditory development in humans. The molecular basis underlying the susceptibility of auditory cortex to loss of afferent input remains largely unknown. The transcription factor early growth response-1 (EGR-1) expression in the visual cortex has been shown to be crucial in the formation of vision, but the role of EGR-1 during the process of auditory function formation is still unclear. In this study, we presented data showing that EGR-1 was expressed in the neurons of the primary auditory cortex (A1) in mice. We observed that the auditory deprivation induced by kanamycin during the auditory critical period leads to laminar-specific alteration of neuronal distribution and EGR-1 expression in A1. In addition, MK-801 administration inhibited the expression of EGR-1 in A1 and aggravated the abnormal cortical electric response caused by kanamycin injection. Finally, we showed that the expression of PI3K, the phosphorylation of Akt, as well as the phosphorylation of cAMP-responsive element-binding protein (CREB) were decreased in A1 after kanamycin-induced hearing loss. These results characterized the expression of EGR-1 in A1 in response to the acoustic input and suggested the involvement of EGR-1 in auditory function formation.

Efficacy of surgical repair for the functional restoration of injured facial nerve.

BACKGROUND: Early surgical repair to restore nerve integrity has become the most commonly practiced method for managing facial nerve injury. However, the evidence for the efficacy of surgical repair for restoring the function of facial nerves remains deficient. This study evaluated the outcomes of surgical repair for facial nerve lesions. METHODS: This retrospective observational study recruited 28 patients with the diagnosis of facial nerve injury who consecutively underwent surgical repairs from September 2012 to May 2019. All related clinical data were retrospectively analyzed according to age, sex, location of the facial nerve lesion, size of the facial nerve defect, method of repair, facial electromyogram, and blink reflex. Facial function was then stratified with the House-Brackmann grading system pre-operation and 3, 9, 15, and 21 months after surgical repair. RESULTS: The 28 patients enrolled in this study included 17 male and 11 female patients with an average age of 34.3 ± 17.4 years. Three methods were applied for the repair of an injured facial nerve, including great auricular nerve transplantation in 15 patients, sural nerve grafting in 7 patients, and hypoglossal to facial nerve anastomosis in 6 patients. Facial nerve function was significantly improved at 21 months after surgery compared with pre-operative function (P = 0.008). Following surgical repair, a correlation was found between the amplitude of motor unit potential (MUP) and facial nerve function (r = -6.078, P = 0.02). Moreover, the extent of functional restoration of the facial nerve at 21 months after surgery depended on the location of the facial nerve lesion; lesions at either the horizontal or vertical segment showed significant improvement(P = 0.008 and 0.005), while no functional restoration was found for lesions at the labyrinthine segment (P = 0.26). CONCLUSIONS: For surgical repair of facial nerve lesions, the sural nerve, great auricular nerve, and hypoglossal-facial nerve can be grafted effectively to store the function of a facial nerve, and MUP may provide an effective indicator for monitoring the recovery of the injured nerve.

Regulation of Spiral Ganglion Neuron Regeneration as a Therapeutic Strategy in Sensorineural Hearing Loss.

In the mammalian cochlea, spiral ganglion neurons (SGNs) are the primary neurons on the auditory conduction pathway that relay sound signals from the inner ear to the brainstem. However, because the SGNs lack the regeneration ability, degeneration and loss of SGNs cause irreversible sensorineural hearing loss (SNHL). Besides, the effectiveness of cochlear implant therapy, which is the major treatment of SNHL currently, relies on healthy and adequate numbers of intact SGNs. Therefore, it is of great clinical significance to explore how to regenerate the SGNs. In recent years, a number of researches have been performed to improve the SGNs regeneration strategy, and some of them have shown promising results, including the progress of SGN regeneration from exogenous stem cells transplantation and endogenous glial cells' reprogramming. Yet, there are challenges faced in the effectiveness of SGNs regeneration, the maturation and function of newly generated neurons as well as auditory function recovery. In this review, we describe recent advances in researches in SGNs regeneration. In the coming years, regenerating SGNs in the cochleae should become one of the leading biological strategies to recover hearing loss.

Planar cell polarity defects and hearing loss in sperm-associated antigen 6 (Spag6)-deficient mice.

Spag6 encodes an axoneme central apparatus protein that is required for normal flagellar and cilia motility. Recent findings suggest that Spag6 also plays a role in ciliogenesis, orientation of cilia basal feet, and planar polarity. Sensory cells of the inner ear display unique structural features that underlie their mechanosensitivity. They represent a distinctive form of cellular polarity, known as planar cell polarity (PCP). However, a role for Spag6 in the inner ear has not yet been explored. In the present study, the function of Spag6 in the inner ear was examined using Spag6-deficient mice. Our results demonstrate hearing loss in the Spag6 mutants, associated with abnormalities in cellular patterning, cell shape, stereocilia bundles, and basal bodies, as well as abnormally distributed Frizzled class receptor 6 (FZD6), suggesting that Spag6 participates in PCP regulation. Moreover, we found that the subapical microtubule meshwork was disrupted. Our observations suggest new functions for Spag6 in hearing and PCP in the inner ear.

Dexamethasone protects the hearing of Meniere's disease patients after triple semicircular canal plugging.

Background: TSCP has shown its efficacy in vertigo control for intractable Meniere's disease. However, hearing impairment remains a problem and hampered the application of the surgery.Aims/objectives: To investigate the effect of dexamethasone on the hearing of Meniere's disease patients after TSCP to determine whether inflammation is involved in this processMaterial and methods: Meniere's disease patients who received TSCP surgeries were treated with or without dexamethasone postoperatively. All patients' hearing function were evaluated during a follow up of 2 years after surgery and compared between the two groups.Results: Hearing worsening and word recognition score loss were milder in the dexamethasone group than in the non-dexamethasone group. The rates of profound hearing worsening and word recognition score loss remained significantly lower in the dexamethasone group than in the non-dexamethasone group even 2 years after surgery.Conclusions: Dexamethasone protects the hearing of Meniere's patients after TSCP. Inflammation may be involved in the mechanism by which TSCP causes hearing impairment in these patients.Significance: This finding suggests that steroids should be used routinely after TSCP for hearing preservation, and operative precedures need to be modified to minimize inflammation in the inner ear.

Platelet-rich plasma can release nutrient factors to promote facial nerve crush injury recovery in rats.

OBJECTIVES: To evaluate the effects of platelet-rich plasma (PRP) on promoting neural repair after facial nerve compression in rats and the mechanism by which this occurs.  Methods: Adult Wistar rats (n=100) were divided into 3 groups: healthy controls, surgery-only, and surgery+PRP groups. The rats underwent nerve crush injury to establish a facial palsy model. The blood from the rats was used to prepare the PRP for application to the injury site. The evaluation methods included vibrissae movement, eyelid closure, and electrophysiology. Electron microscopy, immunohistochemistry, and real-time polymerase chain reaction (PCR) were used to detect nutrient factor expression in the brain and nerve sections. This study was conducted in Shandong Provincial ENT Hospital Affiliated to Shandong University,  Shandong, China between January and November 2018.  Results: Platelet-rich plasma promotes the recovery of vibrissae movement, eyelid closure, and electrophysiological function in a rat model of nerve crush injury. Hematoxylin and eosin staining, toluidine blue staining, and electron microscopy showed significant recovery of Schwann cells and axons in the PRP group. Polymerase chain reaction results showed that PRP releases growth factors, which include nerve growth factor and brain-derived neurotrophic factor. Immunohistochemistry also demonstrated higher levels of S-100 protein expression in the PRP group compared to the other groups.  Conclusions: Platelet-rich plasma releases nutrient factors in the brainstem, and the use of PRP can promote injury recovery.

Revision surgery after triple semicircular canal plugging and morphologic changes of vestibular organ.

This study aims to investigate the causes of vertigo relapse in patients with Meniere's disease (MD) who had undergone triple semicircular canal plugging (TSCP) and explore the morphologic changes of vestibular organ through revision surgery. Eleven intractable MD patients who underwent TSCP initially and experienced episodic vertigo recurrence later, were enrolled. All patients accepted revision surgery, including seven cases who underwent labyrinthectomy and four cases who underwent repeat TSCP. Pure tone test, caloric test and video-head impulse test (v-HIT) were used to evaluate audiological and vestibular functions. Specimens of canal plugging materials and vestibular end organs were collected from patients who underwent labyrinthectomy during revision surgery. Mineralization and other histological characteristics of canal plugging materials were evaluated by von Kossa staining. Incomplete occlusion or ossification was observed in the semicircular canals (SCs) of all eleven patients, with all three SCs affected in three, the superior SC in five patients, the horizontal SC in two and the posterior SC in one. The results of v-HIT were in accordance with findings discovered intraoperatively. Few mineralized nodules and multiple cavities were found in the von Kossa-stained canal plugging materials. Incomplete occlusion or ossification of SCs was the principal cause of vertigo recurrence in MD patients who underwent TSCP. v-HIT was helpful in determining the responsible SCs.

Wnt Signaling Protects against Paclitaxel-Induced Spiral Ganglion Neuron Damage in the Mouse Cochlea In Vitro.

It has been reported that paclitaxel administration could cause sensorineural hearing loss, and Wnt activation is important for the development and cell protection of mouse cochlea. However, the effect of Wnt signaling in spiral ganglion neurons (SGNs) damage induced by paclitaxel has not yet been elucidated. In this study, we explored the effect of paclitaxel on SGNs in the mouse cochlea and the neuroprotective effects of Wnt signaling pathway against paclitaxel-induced SGN damage by using Wnt agonist/antagonists in vitro. We first found that paclitaxel treatment resulted in a degenerative change and reduction of cell numbers in SGNs and induced caspase-mediated apoptosis in SGNs. The expression levels of ß-catenin and C-myc were increased, thus indicating Wnt signaling was activated in SGNs after paclitaxel treatment. The activation of Wnt signaling pathway protected against SGN loss after exposure to paclitaxel, whereas the suppression of Wnt signaling in SGNs made them more vulnerable to paclitaxel treatment. We also showed that activation of Wnt signaling in SGNs inhibited caspase-mediated apoptosis. Our findings demonstrated that Wnt signaling had an important role in protecting SGNs against paclitaxel-induced damage and thus might be an effective therapeutic target for the prevention of paclitaxel-induced SGN death.

Long-term outcomes of triple semicircular canal plugging for the treatment of intractable Meniere's disease: A single center experience of 361 cases.

INTRODUCTION: Meniere's disease is a common chronic inner ear disease. Because the definitive pathogenesis is still unknown, there is currently no cure for this disorder. Semicircular canal plugging (SCP), first used to treat patients with intractable benign paroxysmal positional vertigo, has since been applied to patients with intractable peripheral vertigo. This study was aimed to explore the long-term efficacy of triple semicircular canal plugging (TSCP) in the treatment of intractable Meniere's disease (MD) so as to provide a new method in the framework of treatment with MD. METHODS: Three hundred and sixty-one unilateral MD patients, who were treated with TSCP in our hospital between Dec. 2010 and Sep. 2016, were recruited in this study for retrospective analysis. Vertigo control and auditory function were monitored during a period of two-year follow-up. Seventy three patients who were subjected to intratympanic gentamicin were selected as a control group. Pure tone audiometry, caloric test, vestibular evoked myogenic potential (VEMP) were performed in two-year follow-up. RESULTS: The total control rate of vertigo in TSCP group was 97.8% (353/361) in the two-year follow-up, with complete control rate of 80.3% (290/361) and substantial control rate of 17.5% (63/361). The rate of hearing loss was 26.3% (95/361). The total control rate of vertigo in intratympanic gentamicin group was 83.6% (61/73), with complete control rate of 63.0% (46/73) and substantial control rate of 20.5% (15/73). The rate of hearing loss was 24.7% (18/73). The vertigo control rate of TSCP was significantly higher than that of chemical labyrinthectomy(χ2 = 24.798, p <  0.05). There was no significant difference of hearing loss rate between two groups. (χ2 = 0.087, p >  0.05). CONCLUSION: Triple semicircular canal plugging (TSCP), which can reduce vertiginous symptoms in patients with intractable Meniere's disease (MD), represents an effective therapy for this disorder. It might become a new important method in the framework of treatment with MD.

Allicin Protects against Cisplatin-Induced Stria Vascularis Damage: Possible Relation to Inhibition of Caspase-3 and PARP-1-AIF-Mediated Apoptotic Pathways.

Cisplatin is an anti-cancer drug that causes oxotoxic side effects such as impairment of inner ear function and hearing loss. We aimed to investigate the effects of allicin against cisplatin-induced stria vascularis damage in mice, and to clarify the mechanism underlying the protective effects of allicin against ototoxicity. Stria vascularis injury was induced in mice by intraperitoneal injection of cisplatin, which was significantly prevented by pretreatment with allicin. Allicin not only reduced cisplatin-activated expression of cleaved caspase-3 in marginal cells, PVM/Ms (perivascular resident macrophage-like melanocytes), and basal cells of the stria vascularis, but also decreased the expression of poly(ADP-ribose) polymerase-1 (PARP-1) and apoptosis-inducing factor (AIF) nuclear translocation in the stria vascularis cells. Our results demonstrate that allicin plays an effective role in protecting stria vascularis injury induced by cisplatin by inhibiting caspase-dependent, as well as caspase-independent PARP-1-AIF-mediated apoptotic pathways. Therefore, allicin may be useful in preventing cisplatin-induced ototoxicity.