Objective:To investigate the impact of Waardenburg syndrome（WS） -associated Sox10 p.S100Rfs*9 mutation on inner ear function and its mechanism in noise-induced hearing impairment. Methods:A mice model carrying the Sox10 p.S100Rfs*9 mutation was established using CRISPR-Cas9 gene editing technology. Auditory phenotypes were assessed under baseline conditions and after noise exposure（96 dB SPL, 2 hours）. Auditory brainstem response（ABR） tests were performed to evaluate hearing function, combined with immunofluorescence staining of cochlear basilar membrane whole-mounts to observe hair cells and ribbon synapses. Transcriptome sequencing was conducted to analyze molecular mechanisms. Results:Sox10 p.S100Rfs*9 heterozygous mice exhibited normal hearing thresholds with characteristic ventral pigmentation abnormalities under baseline conditions. Following noise exposure, mutant mice showed significantly higher ABR thresholds at 24 000 Hz compared to wild-type controls（[60.00±6.12]vs[48.13±4.28]dB SPL, P<0.000 1）, and a significant reduction in ribbon synapses（CtBP2-positive puncta） in the basal turn（[55.0±2.3]vs[64.8±3.3]per inner hair cell, P=0.006 6）, while hair cell morphology and number remained intact. Transcriptome analysis revealed altered expression of genes involved in immune regulation, membrane structures, ion channels, and neuroactive ligand-receptor interactions. Conclusion:The Sox10 p.S100Rfs*9 mutation does not alter baseline hearing function but significantly increases inner ear susceptibility to noise damage, primarily manifested as enhanced ribbon synapse vulnerability, especially in high-frequency regions. This gene-environment interaction reveals that Sox10 haploinsufficiency may compromise noise tolerance by affecting synaptic stability and inner ear protective mechanisms. These findings provide new perspectives on the phenotypic heterogeneity in WS patients and theoretical basis for individualized noise protection strategies for patients carrying SOX10 mutations.
Animals ; SOXE Transcription Factors/genetics* ; Waardenburg Syndrome/physiopathology* ; Mice ; Hearing Loss, Noise-Induced/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Mutation ; Noise ; Disease Models, Animal ; Ear, Inner/physiopathology*

Objective:To explore of auditory-vestibular function and inner ear imaging features of patients with Meniere's disease（MD） at different clinical stages. Methods:The clinical data of 110 patients with unilateral MD who were admitted from January 2023 to March 2024 were collected, and all patients were staged according to the results of pure tone hearing threshold test, including 13 patients with stage Ⅰ, 18 cases with stage Ⅱ, 65 cases with stage Ⅲ, and 14 cases with stage Ⅳ. All patients were tested for vestibular function, including caloric tests, vestibular evoked myogenic potentials（VEMPs）, vHIT and sensory integration tests（SOT）. The sites of endolymphatic hydrops were evaluated by intravenous endotogidolinium-based MRI, twenty-seven patients completed electrocochleography. Results:①The disease course time of patients with different stages was different, and the disease course time of stage Ⅰ and Ⅱ was shorter than that of stage Ⅲ and Ⅳpatients（P<0.05）. ②No statistical differences were found in clinical data or vestibular function between normal and abnormal ECochG groups（P>0.05）. ③The results of caloric tests showed that the UW% values of stage Ⅲ（45.5±14.79） and stage Ⅳ （51.57±22.44） were higher than those of stageⅠ（31.2±14.9） and stage Ⅱ（33.5±13.31）, there were statistically significant differences between stage Ⅰ and stage Ⅱ with stage Ⅲ and Ⅳ groups（P<0.05）, the total abnormal rate of cVEMP was 62.72%, there was a statistically significant difference between stageⅠand stage Ⅲ with the stage Ⅳ group（P<0.05）, the total abnormal rate of oVEMP was 71.82%, the difference between stage Ⅰ and stage Ⅳ group was statistically significant（P<0.05）. The total score of SOT comprehensive balance gradually decreased with the increase of clinical stage, and there was a significant difference between the stage Ⅰ and Ⅳ groups（H=26.08, P<0.01）, and there was a statistically significant difference in the rate of vestibular dysfunction of SOT between the two groups（χ²=6.7, P<0.05）. ④Patients with vestibular and cochlear endolymphatic hydrops, and patients with simple cochlear or vestibular had significantly differences in disease course time, clinical stages, UW% value of caloric test, abnormal rate of cVEMP and oVEMP, total SOT balance score, the rate of vestibular abnormality（P<0.01）. Among them, when the vestibular and cochlear endolymphatic hydrops are at the same time, the clinical stage of the patient is mainly stage Ⅲand Ⅳ. Conclusion:Auditory-vestibular and inner ear gadolinium-contrasted MRI examinations in clinical practice provide a supplementary reference for judging vestibular function and the type of endolymphatic hydrops.
Humans ; Meniere Disease/diagnostic imaging* ; Ear, Inner/physiopathology* ; Male ; Magnetic Resonance Imaging ; Female ; Middle Aged ; Vestibule, Labyrinth/diagnostic imaging* ; Adult ; Vestibular Evoked Myogenic Potentials ; Aged ; Audiometry, Pure-Tone ; Caloric Tests ; Vestibular Function Tests

Objective: The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae. Methods: Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity. Results: The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml Conclusion This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.
Animals ; Ear, Inner/growth & development* ; Embryo, Nonmammalian/drug effects* ; Gene Expression Regulation, Developmental/drug effects* ; Hair Cells, Auditory/metabolism* ; Lateral Line System/growth & development* ; Locomotion/drug effects* ; Ototoxicity/physiopathology* ; Toluene/toxicity* ; Zebrafish

Ear, Inner ; physiopathology ; surgery ; Humans ; Vertigo ; surgery

OBJECTIVE: To investigate the intra-operative electrical evoked auditory brain stem response (EABR) characteristics and the hearing and speech rehabilitation effects of cochlear implantation (CI) in patients with internal auditory canal stenosis (IACS). METHOD: A retrospective study was performed on 16 patients with IACS (IACS group) matched with 16 implanted without IACS (control group), who received multi- channel CI because of pre-lingual sensorineural hearing loss. The integrity and functional status of the auditory pathway were assessed by EABR, recording waveforms, thresholds and dynamic ranges intra-operation before CI. Interviewed the implanted parents or teachers, asking them to rate the implanted hearing and speech ability according to Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR). Paired T test was performed to compare scores of CAP and SIR between before and 1 year after CI, while Spearman test was performed to compare correlation between EABR grades and post-operative CAP scores. RESULT: Among the IACS group, 2 cases weren't recorded typical EABR waveforms and without auditory response 1 year after a successful CI. The EABR waveforms in the IACS group were poorer than that in the control group, their EABR thresholds higher than the control group, and their EABR dynamic ranges less than the control group. The hearing and speech rehabilitation after CI showed that the results of CAP and SIR values (3.47 +/- 1.09 and 1.62 +/- 0.50) scored significantly lower than the control group (5.06 +/- 0.79 and 2.59 +/- 0.58) (P < 0.05), but significantly increased compared with pre-operation. Intra-operative EABR grades and post-operative CAP scores showed significant correlation (r = 0.78 , P < 0.05). CONCLUSION Intra-operative EABR can accurately monitor the integrity and functional status of the auditory pathway, be of important clinical value in predicting whether patients can acquire auditory responses with the aid of CI. CI can help patients with IACS to improve the ability of hearing and speech with EABR to screen out compatible implanted.
Adolescent ; Auditory Pathways ; Child ; Child, Preschool ; Cochlear Implantation ; Constriction, Pathologic ; Ear, Inner ; surgery ; Evoked Potentials, Auditory, Brain Stem ; Female ; Humans ; Infant ; Labyrinth Diseases ; physiopathology ; surgery ; Male ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVE: To investigate the changes and determine the difference of electrode impedance and neural response telemetry ( NRT) value with cochlear implants in children with malformed inner ear and normal inner ear. METHOD: Eighty-eight children with multi-channel cochlear implants participated in this study. Children were divided into malformed inner ear group and normal inner ear group. To test the electrode impedance values and NRT value. RESULT: The changes of electrode impedance showed the similar changing pattern in two groups. There was not different in electrode impedance values between the two groups (P > 0.05). The changes of electrode neural response telemetry values showed the similar changing pattern in two groups. There was significantly different in electrode impedance values between the two groups (P < 0.05). The NRT were going up higher from electrode 22 to electrode 1. CONCLUSION The values vary are different programming sessions and electrodes during the first 3 months of cochlear implant use. To acquire better hearing frequent programming sessions are necessary.
Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Cochlear Implantation ; Cochlear Implants ; Cochlear Nerve ; Ear, Inner ; abnormalities ; physiopathology ; surgery ; Electric Impedance ; Electrodes ; Female ; Humans ; Infant ; Male

Free radicals are atoms, molecules or ions with unpaired electrons. In biological systems, free radicals can have a dual role, being beneficial in some situations and deleterious in others. Free radicals are required for normal cellular metabolism, but they lead to cellular degeneration if overproduced. To prevent the excessive buildup of free radicals, cells have developed an elaborate series of antioxidant enzymes that counteract oxidative stress and protect cells by maintaining the proper balance of oxidation and anti-oxidation. Therefore, when there is an oxidant/anti-oxidant imbalance, no matter what direction, cells are likely to be damaged. Numerous reports in the literature indicate that free radicals play important roles in diseases of the inner ear as a result of noise exposure, ototoxic drugs, aging, and other pathological conditions. Therefore, there have been many attempts to employ antioxidants treat inner ear damage. However, antioxidant therapy could be harmful if the improper compound or dose is employed. Effective antioxidant therapy requires prior knowledge of the type(s) of oxidative stress occurring in real time in the inner ear. Since most techniques for detecting free radicals in the inner ear are not clinically feasible, systemic anti-oxidant therapy is generally performed "blindly" and therefore likely to disrupt normal antioxidant levels in the inner ear or elsewhere in the body. If only a single anti-oxidant is used to treat a disease, it may disturb subsequent steps the oxidative/anti-oxidative chain reaction. An alternative approach, hydrogen therapy represents a promising therapeutic tool because it can selectively scavenge the strongest oxidant species, the hydroxyl radical and peroxynitrite anion, without disturbing normal oxidant/anti-oxidant cellular processes. In addition, hydrogen has no cytotoxic effects to cells so that it provides a near ideal therapy to eliminate toxic free radicals.
Animals ; Ear, Inner ; metabolism ; physiopathology ; Free Radicals ; metabolism ; Humans ; Oxidative Stress

OBJECTIVE: To analyze the constitute, imaging and auditory characteristics of pediatric patients with congenital malformations of inner ear in sensorineural hearing loss(SNHL). METHOD: Imaging and auditory data of 125 cases (225 ears) in 860 pediatric patients with congenital SNHL who referred to ENT department of Shanghai Children Medical Center from February 2005 to January 2010 were retrospectively studied. RESULT: Congenital malformations of inner ear accounted for 14.5% in 860 pediatric patients with congenital SNHL. Bilateral ear was involved in 98 cases (78.4%), unilateral in 27 cases (21.6%). One hundred and sixty-seven ears (74.2%) were identified as profound deafness, 36 ears (16%) severe deafness and 22 ears (9.8%) moderate deafness in 225 ears, respectively. In present group, large vestibular aqueduct (75.6%) was the most common and next was vestibular deformity (32%), then cochleovestibular deformity (23.1%). Mondini deformity (55.8%) was the most common and common cavity deformity (28.9%) next in cochleovestibular deformity. Profound deafness in cochlea involved congenital malformations of inner ear was significantly more than those in no cochlea involved malformations. CONCLUSION The results are of importance for understanding the constitute of congenital malformations of inner ear in pediatric patients with congenital SNHL in China, for etiological diagnosis of congenital SNHL, for intervention including hearing aids or cochlear implant and prognosis.
Child ; Child, Preschool ; Ear, Inner ; abnormalities ; Female ; Hearing Loss, Sensorineural ; diagnosis ; pathology ; physiopathology ; Hearing Tests ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Retrospective Studies ; Tomography, X-Ray Computed

To understand whether some amino acids in the medial vestibular nucleus (MVN) of conscious rats are involved in the regulation of blood pressure, microdialysis technique and high performance liquid chromatography (HPLC) were used to measure the changes of gamma-aminobutyric acid (GABA) and glycine (Gly) in this central area. Wistar rats (250-350 g) were randomly divided into three experimental groups: the control group with intact labyrinths; the ipsilateral MVN of unilateral labyrinthectomy (UL); contralateral MVN of the UL. Acute hypotension was induced by intravenous infusion of sodium nitroprusside (SNP). Unilateral chemical labyrinthectomy was performed 14 days before the start of the experiment to eliminate afferent signals from the peripheral vestibular receptors in the inner ear. Blood pressure decreased by 30% after SNP injection. In the control group, GABA and Gly release reduced to 43.53%+/-6.58% (P<0.01) and 62.24%+/-7.51% (P<0.01) respectively in the MVN following SNP-induced acute hypotension in conscious rats. In the contralateral MVN of UL, GABA and Gly release also reduced to 45.85%+/-17.27% (P<0.01) and 73.30%+/-3.00% (P<0.01) respectively following SNP-induced acute hypotension in conscious rats. In contrast, in the ipsilateral MVN of UL, GABA and Gly releases were not changed following SNP-induced acute hypotension in conscious rats. These results suggest that the SNP-induced acute hypotension may influence the activity of the neurons in the MVN by the afferent impulses from the peripheral vestibular organ, and that GABA and Gly may be involved in this process.
Acute Disease ; Animals ; Chromatography, High Pressure Liquid ; Ear, Inner ; physiology ; surgery ; Glycine ; metabolism ; Hypotension ; metabolism ; physiopathology ; Male ; Microdialysis ; Random Allocation ; Rats ; Rats, Wistar ; Vestibular Nuclei ; metabolism ; physiology ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVE: To analyse the clinical audiological significance in the diagnosis of large vestibular aqueduct syndrome (LVAS) by the auditory brain stem response (ABR) testing. METHOD: Patients with sensorineural hearing loss were examined by temporal bone CT scanning from January, 2008 to September, 2009. The result of CT scanning of 70 cases inner ear malformation were analysed. Patients were divided into two groups, LVAS group including 38 cases (76 ears) and other inner ear malformation group including 32 cases (62 ears). All patient accepted clinical audiology analysis and auditory brainstem response (ABR) test. RESULT: Twenty-four cases (41 ears) of LVAS group were detected with ASNR in 2 3 cm by the ABR testing, the positive rate was 54%, while ASNR was not detected in patients of other inner ear malformations group. There was significant differences (P=0.01) of the ASNR between two groups. CONCLUSION There is high incidence of LVAS on the patients with non-syndromic deafness. ASNR by ABR testing could help diagnosing the LVAS.
Child ; Child, Preschool ; Ear, Inner ; abnormalities ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Loss, Sensorineural ; diagnosis ; physiopathology ; Humans ; Infant ; Infant, Newborn ; Male ; Syndrome ; Vestibular Aqueduct ; abnormalities