The morphological and functional development of the stria vascularis in miniature pigs.

The purpose of this study was to examine the morphological and functional development of the lateral wall of the scala media of the cochlea in miniature pigs; light and transmission electron microscopy and electrophysiology were used for this purpose. We showed that the lateral wall of the scala media of the cochlea appears at embryonic Day 21 (E21) when the cochlear duct begins to form. From E28 to E49, the lateral wall can be distinguished according to its position along the cochlea. At E56, cells in the lateral wall begin to differentiate into three different types. At E70, three cell types, marginal, intermediate and basal, can be clearly distinguished. At E91, the stria vascularis is adult-like and the organ of Corti is also morphologically mature. The average endocochlear potential measured from the second turn of the cochlea (at E98, postnatal Day 1 (P1), P13 and P30) was 71.4±2.5 (n=7), 78.8±1.5 (n=10), 77.3±2.3 (n=10) and 78.0±2.1 mV (n=10), respectively. Our results suggest that in miniature pigs the stria vascularis develops during the embryonic period, concurrent with maturation of the organ of Corti. The magnitude of the endocochlear potential reached its mature level when the stria vascularis was morphologically adult-like at E98. These findings provide a morphological and functional basis for future animal studies using the miniature pig model concerning the pathogenesis of various inner-ear diseases.

A de novo silencer causes elimination of MITF-M expression and profound hearing loss in pigs.

BACKGROUND: Genesis of novel gene regulatory modules is largely responsible for morphological and functional evolution. De novo generation of novel cis-regulatory elements (CREs) is much rarer than genomic events that alter existing CREs such as transposition, promoter switching or co-option. Only one case of de novo generation has been reported to date, in fish and without involvement of phenotype alteration. Yet, this event likely occurs in other animals and helps drive genetic/phenotypic variation. RESULTS: Using a porcine model of spontaneous hearing loss not previously characterized we performed gene mapping and mutation screening to determine the genetic foundation of the phenotype. We identified a mutation in the non-regulatory region of the melanocyte-specific promoter of microphthalmia-associated transcription factor (MITF) gene that generated a novel silencer. The consequent elimination of expression of the MITF-M isoform led to early degeneration of the intermediate cells of the cochlear stria vascularis and profound hearing loss, as well as depigmentation, all of which resemble the typical phenotype of Waardenburg syndrome in humans. The mutation exclusively affected MITF-M and no other isoforms. The essential function of Mitf-m in hearing development was further validated using a knock-out mouse model. CONCLUSIONS: Elimination of the MITF-M isoform alone is sufficient to cause deafness and depigmentation. To our knowledge, this study provides the first evidence of a de novo CRE in mammals that produces a systemic functional effect.

Sudden Sensorineural Hearing Loss Before COVID-19, During COVID-19, and After Inactivated Vaccination: Experience From a Tertiary Referral Center in China.

OBJECTIVE: The purpose of this study was to investigate the incidence rate and audiological characteristics of sudden sensorineural hearing loss (SSHL) before the COVID-19 pandemic, during the COVID-19 pandemic, and after inactivated vaccination, and to analyze whether the novel coronavirus or inactivated vaccination have an impact on hearing loss. MATERIALS AND METHODS: The clinical data of all patients who visited the hospital in July 2019 (before pandemic), July 2020 (during pandemic) and July 2021 (after the inactivated vaccination at least the first basic dose of COVID-19 vaccination) were retrospective analyzed. All patients diagnosed with sudden sensorineural hearing loss in these three periods were screened, and their incidence rate, hearing characteristics, and prognosis were compared. RESULTS: Overall, the incidence rates of sudden hearing loss in July 2019, July 2020, and July 2021 were 0.59, 0.60, and 0.52% (25 of 4225, 20 of 3322, 28 of 5432), respectively, without significant difference (χ2 = 0.372, p = 0.830). A significant difference was noted in the incidence of hypertension (p = 0.02), whereas no significant difference was noted in age (p = 0.591, p = 0.66), sex (p = 0.19, p = 0.08), main symptoms (p = 0.18, p = 0.15), side (p = 0.483, p = 0.89), audiogram shape (p = 0.56, p = 0.989), average hearing threshold of affected frequency (p = 0.81, p = 0.89), average hearing threshold of normal ear affected frequency (p = 0.65, p = 0.68), average hearing threshold of affected frequency after treatment (p = 0.49, p = 0.38), days between symptoms onset and hospital visit (p = 0.62, p = 0.85), treatment plan (p = 0.551, p = 0.474), and effectiveness (p = 0.104, p = 0.050). CONCLUSION: Our study failed to find a correlation between the novel coronavirus pandemic and inactivated vaccination and SSHL, and there was no direct evidence supporting that COVID-19 or inactivated vaccination had an impact on the incidence rate and prognosis of SSHL patients.

Modified intratympanic steroid therapy for sudden sensorineural hearing loss via tympanic tube and gelfoam as a salvage treatment.

Background: Sudden sensorineural hearing loss (SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy (IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy (SST). Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors. Methods: Totally, 74 patients who were aged 22-81 years with SSNHL were enrolled and allocated to either the control group (n = 25) or the treatment group (n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2-6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST. Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies (250-8000 Hz) compared with the control group (P < 0.05). The findings indicated the duration from the onset of SSNHL to the beginning of IST as an independent factor for pure tone average improvement after treatment (P = 0.002), whereas age, duration of SST, and time of IST were not (P > 0.05). Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL.

Automatic Recognition of Auditory Brainstem Response Waveforms Using a Deep Learning-Based Framework.

OBJECTIVE: Recognition of auditory brainstem response (ABR) waveforms may be challenging, particularly for older individuals or those with hearing loss. This study aimed to investigate deep learning frameworks to improve the automatic recognition of ABR waveforms in participants with varying ages and hearing levels. STUDY DESIGN: The research used a descriptive study design to collect and analyze pure tone audiometry and ABR data from 100 participants. SETTING: The research was conducted at a tertiary academic medical center, specifically at the Clinical Audiology Center of Tsinghua Chang Gung Hospital (Beijing, China). METHODS: Data from 100 participants were collected and categorized into four groups based on age and hearing level. Features from both time-domain and frequency-domain ABR signals were extracted and combined with demographic factors, such as age, sex, pure-tone thresholds, stimulus intensity, and original signal sequences to generate feature vectors. An enhanced Wide&Deep model was utilized, incorporating the Light-multi-layer perceptron (MLP) model to train the recognition of ABR waveforms. The recognition accuracy (ACC) of each model was calculated for the overall data set and each group. RESULTS: The ACC rates of the Light-MLP model were 97.8%, 97.2%, 93.8%, and 92.0% for Groups 1 to 4, respectively, with a weighted average ACC rate of 95.4%. For the Wide&Deep model, the ACC rates were 93.4%, 90.8%, 92.0%, and 88.3% for Groups 1 to 4, respectively, with a weighted average ACC rate of 91.0%. CONCLUSION: Both the Light-MLP model and the Wide&Deep model demonstrated excellent ACC in automatic recognition of ABR waveforms across participants with diverse ages and hearing levels. While the Wide&Deep model's performance was slightly poorer than that of the Light-MLP model, particularly due to the limited sample size, it is anticipated that with an expanded data set, the performance of Wide&Deep model may be further improved.

Analysis of cognitive function and its related factors after treatment in Meniere's disease.

A growing body of research recently suggested the association between vestibular dysfunction and cognitive impairment. Meniere's disease (MD), a common clinical vestibular disorder, is usually accompanied by hearing loss and emotional stress, both of which may mediate the relationship between vestibule dysfunction and cognition. It is currently unknown whether the cognitive decline in MD patients could improve through treatment and how it relates to multiple clinical characteristics, particularly the severity of vertigo. Therefore, in the present study, the MD patients were followed up for 3, 6, and 12 months after treatment, and the cognitive functions, vertigo symptoms, and related physical, functional, and emotional effects of the patients were assessed using the Montreal Cognitive Assessment (MoCA) and Dizziness Handicap Inventory (DHI), aiming to explore the change in cognition before and after therapy and the correlation with various clinical features. It was found that cognitive decline in MD patients compared to healthy controls before therapy. Importantly, this cognitive impairment could improve after effective therapy, which was related to the severity of vertigo, especially in functional and physical impacts. Our results support the view that vestibular dysfunction is a potentially modifiable risk factor for cognitive decline.

Molecular mechanisms and roles of inflammatory responses on low-frequency residual hearing after cochlear implantation.

Preservation of low-frequency residual hearing is very important for combined electro-acoustic stimulation after cochlear implantation. However, in clinical practice, loss of low-frequency residual hearing often occurs after cochlear implantation and its mechanisms remain unclear. Factors affecting low-frequency residual hearing after cochlear implantation are one of the hot spots in current research. Inflammation induced by injury associated with cochlear implantation is deemed to be significant, as it may give rise to low-frequency residual hearing loss by interfering with the blood labyrinth barrier and neural synapses. Pathological changes along the pathway for low-frequency auditory signals transmission may include latent factors such as damage to neuroepithelial structures, synapses, stria vascularis and other ultrastructures. In this review, current research on mechanisms of low-frequency residual hearing loss after cochlear implantation and possible roles of inflammatory responses are summarized.

Middle Ear Surgeries for Chronic Otitis Media Improve Cognitive Functions and Quality of Life of Age-Related Hearing Loss Patients.

Age-related hearing loss (ARHL) may limit communication, which is closely associated with cognitive decline of the elderly and negatively affects their quality of life. In ARHL patients who suffer chronic otitis media (COM), hearing impairment may worsen and negatively affect the cognition and quality of life. It is currently unknown whether restoration of the conductive hearing in the mixed hearing loss through middle ear surgeries can improve both the cognitive function and quality of life of the ARHL patients. Therefore, in the present study, the ARHL patients were followed up for 6 months after middle ear surgeries for COM, and both the cognitive functions and quality of life of the patients were assessed using Montreal Cognitive Assessment and Glasgow Benefit Inventory. It was found that both the cognitive functions and quality of life were improved 6 months after middle ear surgeries. In conclusion, hearing recovery after middle ear surgeries could improve cognitive functions and quality of life of ARHL patients with COM, and surgical intervention is, hence, recommended for COM.

Audiological characteristics and exploratory treatment of a rare condition of acute-otitis-media-associated sudden sensorineural hearing loss.

BACKGROUND: Acute otitis media (AOM) is a common disease that is more prevalent in children. Most studies concerning AOM-associated sudden sensorineural hearing loss are case reports and retrospective in nature, hence the etiology of AOM-associated sudden hearing loss has not been fully established. AIM: To analyze audiological characteristics of AOM-associated sudden hearing loss and evaluate efficacy of combined tympanostomy tube placement (TTP) and intratympanic methylprednisolone. METHODS: Eight adult patients who were diagnosed with AOM-associated sudden hearing loss and ineffectively treated by conventional medical therapy were enrolled in this study. Basic data were collected, and pure tone audiometry was performed to assess the audiological characteristics. Combination therapy with TTP and intratympanic methylprednisolone injection was given to the patients. RESULTS: Mixed or sensorineural hearing loss was observed at high frequencies (2-4 kHz). All the cases in this study were cured after TTP and intratympanic methylprednisolone. After treatment, the average hearing threshold at affected frequencies was significantly lower than those in the pretreatment group (P < 0.05) and was similar to that in the healthy ears (P > 0.05). CONCLUSION: AOM rarely induces sudden sensorineural hearing loss. Combination therapy with TTP and intratympanic methylprednisolone injection may be effective after failure of conventional medical treatment.

Clinical Analysis of Intratympanic Injection of Dexamethasone for Treating Sudden Deafness.

INTRODUCTION: A variety of causes may induce sudden deafness. However, it remains challenging to determine the exact cause in a clinic. There is no standard treatment for this disease due to its unclear etiology. OBJECTIVE: The present study aims to investigate the clinical efficacy of the intratympanic injection of dexamethasone for treating sudden deafness. METHODS: A total of 154 patients with sudden deafness were retrospectively analyzed. The evaluation of sudden deafness was based on the AAO-HNS efficacy evaluative criteria. All patients were initially treated within seven days by an intravenous drip of methylprednisolone, vasodilator, and neurotrophic agents. These patients were divided into two groups: the treatment group (91 patients) and the control group (63 patients). Patients in the treatment group were given an intratympanic injection of dexamethasone, while patients in the control group were given conventional vasodilators and neurotrophic treatment. RESULTS: The effective rate in the treatment group was 47.25% (43/91 patients), and this was significantly higher than in the control group (14.29%, 9/63 patients). The adverse reactions in the treatment group included transient pain (7.69%, 7/91), but there was no vertigo in either group. There was one case of tympanic membrane perforation. CONCLUSION: The intratympanic injection of dexamethasone is a better choice for refractory sudden deafness due to its high efficacy and fewer adverse reactions.

The association between the levels of autoimmune related indicators and clinical condition in sudden deafness patients.

BACKGROUND: This study aimed to analyze the abnormal rates of immune related factors in serum of sudden deafness (SD) patients, and to discuss the correlation between these indicators and the degree of pathological changes of SD patients. METHODS: From March 2018 to January 2021, 90 patients with SD who were hospitalized in Beijing Tsinghua Changgeng Hospital were enrolled as participants, and 60 healthy examinees served as the control group. Antinuclear antibody (ANA), anticardiolipin antibody immunoglobulin G (ACA-IgG), anticardiolipin antibody immunoglobulin M (ACA-IgM), and anti-ß-glucoprotein (anti-ß-GP) antibody were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: In the SD group, 43 participants were positive for ANA, while in the control group, only 9 participants were positive for ANA. The titer of antibodies was significantly higher in the SD group than in the control group. The differences in abnormal rates of ACA-IgG, ACA-IgM, and anti-ß-GP antibodies between the SD group and control group were not statistically significant (P>0.05). CONCLUSIONS: The pathogenesis of SD is correlated with autoimmune factors to a certain extent. In the course of clinical treatment, in addition to vasodilation, neurotrophic therapy, and thrombolytic therapy, patients can also be approached from the perspective of autoimmunity, which may achieve more ideal treatment effects.

Effects of endolymphatic sac decompression combined with posterior tympanotomy with local steroids for intractable Meniere's disease.

Background: Endolymphatic sac decompression surgery (ESDS) is commonly used for intractable Meniere's disease, but its effect remains controversial because of the low rate of vertigo control.Objectives: In the present study, we examined ESDS combined with posterior tympanotomy with local steroids as a new therapeutic strategy for intractable Meniere's disease.Materials and methods: This retrospective study enrolled 19 patients with Meniere's disease using ESDS combined with posterior tympanotomy with local steroids between 2015 and 2018. Postoperatively we recorded and evaluated changes in vertigo attack frequency and hearing level.Results: Vertigo episodes decreased from 3.6 ± 3.2 times preoperatively to 0.2 ± 0.5 times postoperatively, with 89.5% complete vertigo control rate. Mean PTA decreased from 40.5 ± 21.3 dB to 39.5 ± 17.5 dB postoperatively, with 21.1% improvement rate.Conclusions and significance: The present findings suggest that ESDS combined with posterior tympanotomy with local steroids could improve clinical results of hearing as well as vertigo control for intractable Meniere's disease.

Surgical treatment of lateral skull base lesions and reconstruction of the skull base: a report of 20 cases.

OBJECTIVE: To investigate the surgical treatment and related experience of lateral skull base lesions. METHODS: In a retrospective, clinical data analysis of 20 patients with lateral skull base diseases, 11 cases with temporal bone space-occupying lesions and intracranial invasion were treated by translabyrinthine surgery, mastoid cavity drainage, or transmastoid surgery to remove the lesion; two cases of cholesteatoma with destruction of tympanic cavity and tympanic sinus canopy with intracranial invasion were treated by extended radical mastoidectomy; seven cases with lateral skull base bone destruction with cerebrospinal fluid otorrhea caused by trauma and deformity were treated by translabyrinth and transmastoid repair. RESULTS: Eleven cases with temporal bone space occupying lesions were resected completely and were without recurrence after surgery. Two cases with intracranial infection secondary to cholesteatoma were rapidly relieved of symptoms without recurrence after radical mastoidectomy. The remaining seven cases of CSF otorrhea included two cases of Mondini malformation and five cases of temporal bone fracture. The leak was stemmed in all seven cases after surgery. CONCLUSION: Surgery is the main therapeutic option for the treatment of lateral skull base diseases. The surgical approach and the type of skull base reconstruction should be selected on an individual case-by-case basis.

Case analysis of temporal bone lesions with facial paralysis as main manifestation and literature review.

OBJECTIVE: This study aims to discuss clinical characteristics, image manifestation and treatment methods of temporal bone lesions with facial paralysis as the main manifestation for deepening the understanding of such type of lesions and reducing erroneous and missed diagnosis. METHODS: The clinical data of 16 patients with temporal bone lesions and facial paralysis as main manifestation, who were diagnosed and treated from 2009 to 2016, were retrospectively analyzed. Among these patients, six patients had congenital petrous bone cholesteatoma (PBC), nine patients had facial nerve schwannoma, and one patient had facial nerve hemangioma. All the patients had an experience of long-term erroneous diagnosis. RESULTS: The lesions were completely excised by surgery. PBC and primary facial nerve tumors were pathologically confirmed. Facial-hypoglossal nerve anastomosis was performed on two patients. HB grade VI was recovered to HB grade V in one patient. The anastomosis failed due to severe facial nerve fibrosis in one patient. Hence, HB remained at grade VI. Postoperative recovery was good for all patients. No lesion recurrence was observed after 1-6 years of follow-up. CONCLUSION: For the patients with progressive or complete facial paralysis, imaging examination should be perfected in a timely manner. Furthermore, PBC, primary facial nerve tumors and other temporal bone space-occupying lesions should be eliminated. Lesions should be timely detected and proper intervention should be conducted, in order to reduce operation difficulty and complications, and increase the opportunity of facial nerve function reconstruction.

Primary tumors of the facial nerve misdiagnosed: a case series and review of the literature.

CONCLUSION: Unusual primary tumors of the facial nerve should be considered in patients with progressive facial paralysis, especially if this is accompanied by hearing loss or vertigo. Misdiagnosis could increase the difficulties of operation, diminish the chance of facial nerve reconstruction, and increase the likelihood of poor reconstructive outcomes. OBJECTIVE: This paper was to determine the characteristics of facial nerve primary tumors misdiagnosed as tumor-free conditions many years prior, and to describe appropriate treatments. METHODS: The cases of 11 Chinese patients with misdiagnosed primary tumors of the facial nerve were reviewed; every one had been misdiagnosed for more than 8 years. All patients presented with progressive or complete facial paralysis and hearing loss, with or without vertigo. The pre- and post-operative images (including CT scans of the temporal bone) and MRI data were reviewed. RESULTS: All tumors were completely resected using the translabyrinthine or transmastoid approach and were confirmed to be primary tumors of the facial nerve. Facial-hypoglossal nerve anastomosis failed because fibrosis developed at the end of the facial nerve in one patient whom this study sought to manage in two stages. One patient accepted facial-hypoglossal nerve anastomosis of two-stage and patient status improved to House-Brackmann (H-B) grade V from H-B grade VI. The other nine patients chose not to undergo reconstruction.

Establishing the standard method of cochlear implant in Rongchang pig.

CONCLUSIONS: In this investigation, a large mammal, Rongchang pigs were used to successfully establish a research platform for cochlear implant study on the routine use of it in clinic. OBJECTIVE: The aim of this study was to establish a standard method of cochlear implant in a large mammal-pig. METHODS: Rongchang pigs were selected, then divided into two groups: normal-hearing group (Mitf +/+) and mutation group with hearing loss (Mitf -/-). Cochlear implants were used and ABR and EABR were recorded. The implanted electrodes were observed by X-ray and HE stains. RESULTS: The success with cochlear implant and the best electrode position could be defined in all animals, the coiling of the cochlea reached 1.5-1.75 turns. Immediately after the operation of cochlear implants, the ABR threshold of the operated ear (right) could not be derived for each frequency at 120 dB SPL. Moreover, 7 days after surgery, the low-frequency ABR threshold of the operated ear (right) could be derived partly at 100 dB SPL, but the high-frequency ABR threshold could not be derived at 120 dB SPL. Immediately or 1 week after cochlear implants, the EABR threshold was 90 CL in the Mitf +/+ group. This was obviously lower than the 190 CL in the Mitf -/- group.

Miniature pigs: a large animal model of cochlear implantation.

The objective of this paper was to investigate the suitability of the miniature pig as a large animal model of cochlear implantation (CI). Micro-CT scanning and three-dimensional reconstructions of the inner ear were completed in six animals. Photographs of the procedures and measurements of the inner ear were made. The CI procedure was simulated in 10 animals. Electrically evoked auditory brain stem responses (EABRs) and radiographic images were evaluated during or after the CI procedure. Morphological examination and measurements of inner ears of the miniature pigs were completed by micro-CT scanning. The height of the scala tympani was 873.12 µm in the 1st turn, 641.46 µm in the 2nd turn, 445.13 µm in the third turn and 339.19 µm in the fourth turn. The length of the cochlea was 38.6 mm, larger than other animal models (7.2 mm in rats and 22 mm in macaque, for example) and similar to that in the human (36 mm). Commercial electrodes used in humans (870 µm at the end and 630 µm at the tip in diameter) were implanted in the pig's cochlea, through which normal eABRs were obtained. Radiographic images after the CI procedure revealed electrodes located in the scala tympani of the first and second turns. Compared with traditional animal models, greater similarities of the inner ear between miniature pigs and humans make this animal a potentially useful model for CI studies.

Transplantation of human umbilical cord mesenchymal stem cells in cochlea to repair sensorineural hearing.

To examine if transplantation of human umbilical cord mesenchymal stem cells (UMSC) into cochlea can be used to repair sensorineural hearing. Here we transplanted the fifth and sixth generations of UMSCs through the subarachnoid cavity of congenital deaf albino pigs. Auditory brainstem responses (ABR) were measured before and after UMSC transplantation. Cochlear samples were collected at 2 hrs, 3 days, 1, 2, 3, 4 and 8 weeks after transplantation. Immunohistochemistry was used to detect the proliferated cell nuclear antigen (PCNA). The UMSCs were found in different regions of the cochlea, including the stria vascularis, the basal membrane and the spiral ganglions, 3 days to 4 weeks after the transplantation. UMSCs and their DNA were found also in the areas of the brain, the heart, the liver, the kidney and the lung. ABR tests displayed a new waveform in the congenital deaf albino pigs after the UMSCs transplantation. We conclude that human UMSCs injected into the subarachnoid space can migrate into the inner ear, the central nervous system and the periphery organs. The presence of UMSCs in the cochlea maybe associated with changes of ABR waveforms in the congenital deaf albino pigs.

An efficient strategy for establishing a model of sensorineural deafness in rats.

Ototoxic drugs can be used to produce a loss of cochlear hair cells to create animal models of deafness. However, to the best of our knowledge, there is no report on the establishment of a rat deafness model through the combined application of aminoglycosides and loop diuretics. The aim of this study was to use single or combined administration of furosemide and kanamycin sulfate to establish rat models of deafness. The rats received intravenous injections of different doses of furosemide and/or intramuscular injections of kanamycin sulfate. The auditory brainstem response was measured to determine the hearing threshold after drug application. Immunocytochemistry and confocal microscopy were performed to evaluate inner ear morphology. In the group receiving combined administration of furosemide and kanamycin, the auditory brainstem response threshold showed significant elevation 3 days after administration, higher than that produced by furosemide or kanamycin alone. The hair cells showed varying degrees of injury, from the apical turn to the basal turn of the cochlea and from the outer hair cells to the inner hair cells. The spiral ganglion cells maintained a normal morphology during the first week after the hair cells completely disappeared, and then gradually degenerated. After 2 months, the majority of spiral ganglion cells disappeared, but a few remained. These findings demonstrate that the combined administration of furosemide and kanamycin has a synergistic ototoxic effect, and that these drugs can produce hair cell loss and hearing loss in rats. These findings suggest that even in patients with severe deafness, electronic cochlear implants may partially restore hearing.