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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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Can training extend current guidelines for cochlear implant candidacy?

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Neural Regeneration Research 2015年第5期10卷 718-720页

作者： Amal Isaiah Douglas E.H.Hartley Department of Otorhinolaryngology-Head and Neck Surgery University of Maryland School of Medicine National Institute for Health Research (NIHR) Nottingham Hearing Biomedical Research Unit otology and hearing group Division of Clinical NeuroscienceSchool of MedicineUniversity of Nottingham Medical Research Council (MRC) Institute of hearing Research

Since their introduction in the 1960s, cochlear implants （CIS） have undergone several transformations, ulti- mately positioning themselves as the best-performing neural prosthesis available today. They have also been recognized as a unique tool for studying the potential protective effects of patterned electrical stimulation on the developing auditory system, with results from animal models often changing the manner in which CIs are used clinically to deliver auditory information to the brain （Moore and Shannon, 2009）. From the development of the first successful commercial single-channel device, they have evolved into multi-channel devices that are part of the national health programmes of several coun- tries. From the limited speech information provided by the early, rudimentary cochlear implants, these devices are now in a position to deliver intelligible speech infor- mation to the auditory system, largely due to advances in signal processing. Concerted efforts from several dis- ciplines, including engineering, acoustics, neurobiology and otolaryngology have ensured that the continued development of CI technology has resulted in signifi- cant benefits to individuals with profound sensorineural hearing loss.

关键词： Can training extend current guidelines for cochlear implant candidacy CI

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Shrinkage of ipsilateral taste buds and hyperplasia of contralateral taste buds following chorda tympani nerve transection

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Neural Regeneration Research 2015年第6期10卷 989-995页

作者： Yi-ke Li Juan-mei Yang Yi-bo Huang Dong-dong Ren Fang-lu Chi Department of otology and Skull Base Surgery Eye Ear Nose & Throat HospitalFudan University Shanghai Auditory Medical Center Key Laboratory of hearing Science Ministry of Health Department of hearing and Speech Sciences Vanderbilt University

The morphological changes that occur in the taste buds after denervation are not well under- stood in rats, especially in the contralateral tongue epithelium. In this study, we investigated the time course of morphological changes in the taste buds following unilateral nerve transection. The role of the trigeminal component of the lingual nerve in maintaining the structural integrity of the taste buds was also examined. Twenty-four Sprague-Dawley rats were randomly divided into three groups： control, unilateral chorda tympani nerve transection and unilateral chorda tympani nerve transection ＋ lingual nerve transection. Rats were allowed up to 42 days of re- covery before being euthanized. The taste buds were visualized using a cytokeratin 8 antibody. Taste bud counts, volumes and taste receptor cell numbers were quantified and compared among groups. No significant difference was detected between the chorda tympani nerve transection and chorda tympani nerve transection ＋ lingual nerve transection groups. Taste bud counts, volumes and taste receptor cell numbers on the ipsilateral side all decreased significantly compared with control. On the contralateral side, the number of taste buds remained unchanged over time, but they were larger, and taste receptor cells were more numerous postoperatively. There was no evidence for a role of the trigeminal branch of the lingual nerve in maintaining the structural integrity of the anterior taste buds.

关键词： nerve regeneration gustation cytokeratin tongue epithelium immunohistochemistry taste bud trigeminal nerve disorder NSFC grants neural regeneration

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Cell proliferation during hair cell regeneration induced by Math1 in vestibular epithelia in vitro

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Neural Regeneration Research 2018年第3期13卷 497-501页

作者： Yi-bo Huang Rui Ma Juan-mei Yang Zhao Han Ning Cong Zhen Gao Dongdong Ren Jing Wang Fang-lu Chi Department of otology and Skull Base Surgery EYE & ENT Hospital of Fudan University Shanghai China Shanghai Clinical Medical Center of hearing Medicine Shanghai China Key Laboratory of hearing Medicine Ministry of Health Shanghai China

Hair cell regeneration is the fundamental method of correcting hearing loss and balance disorders caused by hair cell damage or loss. How to promote hair cell regeneration is a hot focus in current research. In mammals, cochlear hair cells cannot be regenerated and few vestibular hair cells can be renewed through spontaneous regeneration. However, Math1 gene transfer allows a few inner ear cells to be transformed into hair cells in vitro or in vivo. Hair cells can be renewed through two possible means in birds： supporting cell differentiation and transdifferentiation with or without cell division. Hair cell regeneration is strongly associated with cell proliferation. Therefore, this study explored the relationship between Math1-induced vestibular hair cell regeneration and cell division in mammals. The mouse vestibule was isolated to harvest vestibular epithelial cells. Ad-Math1-enhanced green fluorescent protein （EGFP） was used to track cell division during hair cell transformation.5-Bromo-2′-deoxyuridine （BrdU） was added to track cell proliferation at various time points. Immunocytochemistry was utilized to determine cell differentiation and proliferation. Results demonstrated that when epithelial cells were in a higher proliferative stage, more of these cells differentiated into hair cells by Math1 gene transfer. However, in the low proliferation stage, no BrdU-positive cells were seen after Math1 gene transfer. Cell division always occurred before Math1 transfection but not during or after Math1 transfection, when cells were labeled with BrdU before and after Ad-Math1-EGFP transfection. These results confirm that vestibular epithelial cells with high proliferative potential can differentiate into new hair cells by Math1 gene transfer, but this process is independent of cell proliferation.

关键词： erve regeneration cell proliferation cell division Math1 hair cells hair cell renewal supporting cell differentiation vestibular cells neural regeneration

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Otolithic organ function in patients with profound sensorineural hearing loss

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Journal of otology 2016年第2期11卷 73-77页

作者： Yujuan Zhou Yongzhen Wu Jing Wang Department of otology and Skull Base Surgery Eye Ear Nose & Throat Hospital Fudan University Shanghai Auditory Medical Center Key Laboratory of hearing Science Ministry of Health

Profound sensorineural hearing loss (PSHL) is not uncommonly encountered in otology. In clinics, there is a high incidence of otolithic damage in patients with PSHL, but relevant reports are few. Sharing a continuous membranous structure and similar receptor cell ultrastructures, the cochlea and vestibule may be susceptible to the same harmful factors. Disorders of the inner ear may result in a variety of manifestations, including vertigo, spatial disorientation, blurred vision, impaired articulation, and hearing impairment. Considering the diversity of clinical symptoms associated with PSHL with otolithic dysfunction, it may be frequently misdiagnosed, and objective means of testing the function of otolithic organs should be recommended for hearing-impaired patients. Vestibular-evoked myogenic potentials (VEMPs) via air-conducted sound are of great importance for the diagnosis of otolithic function. hearing devices such as cochlear implants are commonly accepted treatments for PSHL, and early identification and treatment of vestibular disorders may increase the success rate of cochlear implantation. Therefore, it is necessary to increase awareness of otolithic functional states in patients with PSHL.

关键词： Profound sensorineural hearing loss PSHL Otolithic organs Vestibular-evoked myogenic potential VEMP

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Advantages of Short-term Personalized Vestibular Rehabilitation at Home Guided by Professional Therapist for Treatment of Decompensated Vestibular Vertigo

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Current Medical Science 2021年第4期41卷 687-694页

作者： Chen-ru DING Ying-qi GAO Yu-juan ZHOU Jun GU Jing WANG Department of otology and Skull Base Surgery Eye Ear Nose&Throat HospitalFudan UniversityShanghai 200031China Shanghai Auditory Medical Center Shanghai 200031China Key laboratory of hearing Science Ministry of HealthShanghai 200031China

Objective Patients suffered a lot from decompensated vestibular *** and vestibular rehabilitation training have been proven to be effective in prompting vestibular *** rehabilitation training is faced with the challenges of patients’compliance,completion,the average recuperation time and so *** study is aimed to investigate advantages of short-term personalized vestibular rehabihitation at home guided by professional *** A short-term personalized vestibular rehabilitation program(ST-PVR)was designed for patients with decompensated vestibular vertigo in this *** Patients experiencing the ST-PVR program showed significant improvement of Self-Rating Anxiety Scale(SAS),Dizziness Handicap Inventory(DHI),Activities-Specific Balance Confidence Scale(ABC)scores by the second follow-up(at 2nd week after treatment,Pgroup occurred slightly later,DHI for 1 month and SAS for 2 months after treatment(Pgroup was faster than that in the medication *** In general,the short-term PVR program showed great advantages by prompting vestibular compensation quickly and putting forward future direction for clinical treatment on decompensated vestibular vertigo.

关键词： vertigo personalized program medication vestibular compensation therapy vestibular rehabilitation

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A child with severe inner ear malformations with favorable hearing utilization and balance functions after wearing hearing aids

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Journal of otology 2017年第1期12卷 41-46页

作者： Yusuke Kimura Takeshi Masuda Akifumi Tomizawa Hideaki Sakata Kimitaka Kaga National Institute of Sensory Organs National Tokyo Medical Center Tokyo Japan Department of OtolaryngologyeHead and Neck Surgery Nihon University School of Medicine Tokyo Japan Department of Speech Language and Hearing Therapy Mejiro University Saitama Japan Kawagoe otology Institute Saitama Japan

Infants with congenital deafness caused by severe bilateral inner ear malformations frequently suffer from severe hearing loss and poor balance. Unfortunately, the use of hearing aids is usually ineffective in recovering hearing, necessitating cochlear implants. We report a case of a 6-year-old boy with congenital deafness and bilateral inner ear malformations(right side, incomplete partition type I [IP-I]; left side, common cavity deformity). hearing aids had a remarkable effect in this patient, enabling sufficient and favorable hearing recovery such as to allow the patient to engage in daily conversations. Per-rotatory nystagmus was recorded on an electronystagmogram for both right and left rotations in a damped rotational chair test. It is rare for deaf children with severe bilateral inner ear malformation to demonstrate favorable development in hearing and good equilibrium function. Our findings suggest that auditoryevestibular hair cells in this patient may have been partially preserved despite IP-I in the right ear and common cavity deformity of the left ear.

关键词： Congenital hearing loss Inner ear malformations Rotation chair test

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Transient decrease in sound tolerance levels following hearing deprivation in normal-hearing subjects

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Journal of otology 2022年第4期17卷 232-238页

作者： Eleazar Grateron Tricia Scaglione Shriya Airen Stefania Goncalves Sinay A.Ceballos David Baguley Juan A.Chiossone Fundacion Venezolana de Otología Clinical Research GroupVenezuela University of Miami Department of OtolaryngologyUSA University of Nottingham Hearing ScienceUK

Objective:To determine the circadian influence on sound sensitivity produced by temporal hearing deprivation in healthy normal human ***:Participants underwent bilateral earplugging before completion of anthropometry,the author's developed questionnaire,the Hamilton Anxiety and Depression Inventory,pure tone audiometry(PTA),stapedial reflex thresholds(SRT),distortion products otoacoustic emissions input/output(DPOAE-I/O),and uncomfortable loudness levels(ULLs).Afterward,the participants were randomly divided into group A,starting at 8:00 *** finishing at 8:00 p.m.,and group B,starting at 4:00 *** ending at 4:00 *** cortisol levels and audiological test results were obtained at the beginning and end of the session and 24-h free urinary cortisol levels were *** sample:Thirty healthy ***:PTA was 2.68 and 3.33 dB HL in groups A and B,respectively,with no statistical difference between *** were significantly lower in group A compared to group B,with an average of 8.1 dB SPL in group A and 3.3 dB SPL in group B(pgroup A,with no difference in group B,and a night shift in DPOAE-I/O in group ***:Reduced loudness tolerance is demonstrated during daytime hearing deprivation in contrast to nighttime;this may be due to increased central gain in the awake cortex.

关键词： Hyperacusis Central gain hearing deprivation

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Enhanced auditory evoked potentials in musicians:A review of recent findings

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Journal of otology 2016年第2期11卷 63-72页

作者： Himanshu Kumar Sanju Prawin Kumar All India Institute of Speech and hearing Department of Audiology All India Institute of Speech and Hearing

Auditory evoked potentials serve as an objective mode for assessment to check the functioning of the auditory system and *** has reported enhanced electrophysiological responses in musicians, which shows neuroplasticity in musicians. Various databases including Pub Med, Google, Google Scholar and Medline were searched for references related to auditory evoked potentials in musicians from 1994 till date. Different auditory evoked potentials in musicians have been summarized in the present article. The findings of various studies may support as evidences for music-induced neuroplasticity which can be used for the treatment of various clinical disorders. The search results showed enhanced auditory evoked potentials in musicians compared to non-musicians from brainstem to cortical levels. Also, the present review showed enhanced attentive and pre-attentive skills in musicians compared to non-musicians.

关键词： Neuroplasticity Auditory evoked potential Review Musicians Electrophysiological

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Gain adjustment at tinnitus pitch to manage both tinnitus and speech perception in noise

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Journal of otology 2019年第4期14卷 141-148页

作者： Hemanth Narayan Shetty Jijo Mathai Pottackal Department of Audiology All India Institute of Speech and HearingMysuru570006India Department of Speech and hearing JSS Institute of Speech and HearingDharwad580007India

To investigate how much gain variation is required from prescription to effect tinnitus percept,and if this revised prescription affects speech *** participants who experienced catastrophic tinnitus even after fitted with hearing aid were *** were grouped based on their tinnitus pitch and the prescriptive formula used to fit hearing *** were evaluated for handicap from tinnitus using Tinnitus Handicap Inventory(THI).hearing aid was programmed using either NAL-NL2 or DSL(I/o)v5 prescriptive formula and gain at tinnitus pitch was adjusted till the tinnitus get *** 50 was determined soon after fitted with hearing aid and 30 days of hearing aid ***,THI and international outcome inventory for hearing aid(IOI-HA)were determined after 30 days of hearing aid use.A significant higher gain adjustment was needed at tinnitus pitch to reduce tinnitus precept using NAL-NL2 than DSL(I/o)v5 prescriptive ***,SNR 50 was not affected by either tinnitus pitch or revised prescription ***,SNR 50 improved after 30 days of hearing aid use.A 76% of the participants’experienced habituation to perception after 30 days of hearing aid use,10% had slight,10% had mild,and 4% had a moderate degree of tinnitus on *** IOA-HA,96%(N=19)of participants have reported satisfactory,and 4%(N=1)reported moderate benefit from hearing *** of prescriptive formula adjusting gain at tinnitus pitch is an efficient method to reduce tinnitus symptoms and improve speech perception.

关键词： Amplification hearing loss Tinnitus Speech perception hearing aid

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