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Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

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Neural Regeneration Research 2025年第10期20卷 3025-3039页

作者： Jia Fang Zhuangzhuang Li Pengjun Wang Xiaoxu Zhang Song Mao Yini Li Dongzhen Yu Xiaoyan Li Yazhi Xing Haibo Shi Shankai Yin Department of otolaryngology Head and Neck Surgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineOtolaryngology Institute of Shanghai Jiao Tong UniversityShanghai Key Laboratory of Sleep Disordered BreathingShanghaiChina Department of Otorhinolaryngology-Head and Neck Surgery Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial ***,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct *** addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon *** investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with *** found that the mice exhibited auditory deficits following the acute loss of outer hair *** ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over *** profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 *** of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory *** intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury *** findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron *** of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

关键词： degeneration hearing loss macrophages Mcc950 neuroinflammation NLRP3 inflammasome ototoxicity pyroptosis sensorineural hearing loss spiral ganglion neuron

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Diabetic peripheral neuropathy and neuromodulation techniques:a systematic review of progress and prospects

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Neural Regeneration Research 2025年第8期20卷 2218-2230页

作者： Rahul Mittal Keelin McKenna Grant Keith Evan McKenna Joana R.N.Lemos Jeenu Mittal Khemraj Hirani Diabetes Research institute University of Miami Miller School of MedicineMiamiFLUSA Department of otolaryngology University of Miami Miller School of MedicineMiamiFLUSA Herbert Wertheim College of Medicine Florida International UniversityMiamiFLUSA School of Medicine and Public Health University of WisconsinMadisonWIUSA

Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this *** peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and *** aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this *** investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord *** systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral *** the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic *** these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.

关键词： diabetes mellitus diabetic peripheral neuropathy neuromodulation neurostimulation therapy non-pharmacological treatment pain management

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Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleae

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Neural Regeneration Research 2017年第12期12卷 2092-2099页

作者： Wen-wei Luo Zhao Han Dong-dong Ren Xin-wei Wang Fang-lu Chi Juan-mei Yang Department of otolaryngology Eye & ENT Hospital of Fudan University Research institute of otolaryngology Fudan University

Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.

关键词： nerve regeneration Atoh 1 DAPT. transdifferentiation gamma secretase inhibitor cochlea sensory epithelium fetal bovine serum hair cell supporting cell hair cell regeneration neural regeneration

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Clinical applications of free medial tibial flap with posterior tibial artery for head and neck reconstruction after tumor resection

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Chinese Journal of Cancer Research 2017年第3期29卷 231-236页

作者： Qi Zhong Jugao Fang Zhigang Huang Xiaohong Chen Lizhen Hou Yang Zhang Pingdong Li Hongzhi Ma Hongbo Xu Department of otolaryngology Head and Neck Surgery Beijing Tongren Hospital Capital Medical University Beijing institute of otolaryngology Key Laboratory of otolaryngology Head and Neck Surgery (Capital Medical University) Ministry of Education

Tumor resection causes damage in the head and neck which creates problems in swallowing, chewing, articulation, and vision, all of which seriously affect patients' quality of life. In this work, we evaluated the application of a free medial tibial flap in reconstruction of head and neck defects after tumor resection. We discussed the anatomy, surgical technique, and the advantages and disadvantages of the flap. We found several benefits for the flap, such as, it is especially effective for the defects that require thin-layer epithelium to cover or the separated soft tissue defect; a two-team approach can be used because the donor site is far away from the head and neck; and the flap is easy to integrate because of the subcutaneous fat layer of the free medial tibial flap is thin and the flap is soft. Thus, the medial tibial flap could replace the forearm flap for certain applications.

关键词： Head and neck free flap posterior tibial artery reconstruction

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Intra-operative hearing monitoring methods in middle ear surgeries

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Journal of Otology 2016年第4期11卷 -页

作者： Wei Ren Fei Ji Jialing Zeng Hui Zhao Department of otolaryngology/Head and Neck Surgery Chinese PLA Institute of OtolaryngologyChinese PLA General Hospital

Hearing loss is a condition affecting millions of people worldwide. Conductive hearing loss (CHL) is mainly caused by middle ear diseases. The low frequency area is the pivotal part of speech frequencies and most frequently impaired in patients with CHL. Among various treatments of CHL, middle ear surgery is efficient to improve hearing. However, variable success rates and possible needs for prolonged revision surgery still frustrate both surgeons and patients. Nowadays, increasing numbers of researchers explore various methods to monitor the efficacy of ossicular reconstruction intraoperatively, including electrocochleography (ECochG), auditory brainstem response (ABR), auditory steady state response (ASSR), distortion product otoacoustic emissions (DPOAE), subjective whisper test, and optical coherence tomography (OCT). Here, we illustrate several methods used clinically by reviewing the literature.

关键词： Intraoperative monitoring Middle ear surgery Hearing

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Comparison of human nasal epithelial cells grown as explant outgrowth cultures or dissociated tissue cultures in vitro

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Frontiers of Medicine 2013年第4期7卷 486-491页

作者： Jian Jiao Na Meng Hong Wang Luo Zhang Department of otolaryngology Head and Neck SurgeryBeijing Tongren HospitalCapital Medical UniversityBeijing 100005ChinaKey Laboratory of OtolaryngologyHead and Neck Surgery(Ministry of Education)Beijing Institute of OtolaryngologyBeijing 100005China

The purpose of this study was to compare cell growth characteristics,ciliated cell differentiation,and function of human nasal epithelial cells established as explant outgrowth cultures or dissociated tissue *** nasal mucosa of the uncinate process was obtained by endoscopy and epithelial cell cultures were established by explant outgrowth or dissociated tissue culture *** cell growth characteristics were observed by inverted phase contrast *** cell differentiation was detected byβ-tubulin IV and ZO-1 *** and ATP-stimulated ciliary beat frequency(CBF)was measured using a high-speed digital microscopic imaging *** the explant and dissociated tissue cultures established as monolayers with tight junctions and differentiated cell composition,with both types of cultures comprising ciliated and non-ciliated epithelial *** were also frequently found in explant cultures but rarely seen in dissociated tissue *** both culture systems,the highest ciliated cell density appeared at 7th–10th culture day and declined with time,with the lifespan of ciliated cells ranging from 14 to 21 ***,10%of the cells in explant cultures and 20%of the cells in the dissociated tissue cultures were *** two cultures demonstrated similar ciliary beat frequency values at baseline(7.78±1.99 Hz and 7.91±2.52 Hz,respectively)and reacted equivalently following stimulation with 100μM *** results of this study indicate that both the explant outgrowth and dissociated tissue culture techniques are suitable for growing well-differentiated nasal ciliated and non-ciliated cells,which have growth characteristics and ciliary activity similar to those of nasal epithelial cells in vivo.

关键词： ciliated cells ciliary beat frequency dissociated tissue culture explant culture nasal epithelial cells

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Advantages of a miniature pig model in research on human hereditary hearing loss

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Journal of Otology 2015年第3期10卷 105-107页

作者： Weiwei Guo Shi-ming Yang Department of otolaryngology Head & Neck SurgeryInstitute of Otolaryngology of PLAChinese PLA General Hospital

In medical laboratory animals, the pig is the closest species to human in evolution, except for primates. As an animal model, the pig is highly concerned by many scientists, including comparative biology, developmental biology, medical genetics. Rodents as animal model for human hearing defects has are poor producibility and reliability, due to differences in anatomical structure, evolutionary rate and metabolic rate, but these happens to be the advantages of the pig model. In this paper, we will summarize the application of miniature pig in the study of human hereditary deafness.

关键词： Mini pig Animal model Hereditary deafness

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COMBINATIONAL ADMINISTRATION OF AMINOGLYCOSIDES AND LOOP DIURETICS AS AN EFFICIENT STRATEGY TO ESTABLISH DEAFNESS MODELS IN RATS

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Journal of Otology 2014年第2期9卷 91-96页

作者： CONG Tao LIU Riyuan YUAN Shuolong XU Liangwei YANG Shiming Department of otolaryngology Head and Neck surgery Institute of OtolaryngologyChinese PLA General Hospital

It is known that aminoglycoside antibiotics can damage the vestibular and auditory sensory epithelia, and the loop diuretics can enhance the ototoxic effect of aminoglycosides. Previous studies on the synergistic effect of these two types of drugs have used mice, guinea pigs and cats, but not rats. The aim of this study was to determine this synergistic effects in rat cochleae. Rats received intravenous injections of different doses of furosemide and/or intramuscular injections of kanamycin sulfate. Au- ditory brainstem response （ABR）, scanning electron microscopy （SEM） and immunocytochemistry were used to determine the effects of drug administration. In the group receiving combined administration of furosemide and kanamycin, the ABR thresh- old showed significant elevation 3 days after drug administration, greater than single drug administration. The hair cells showed various 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. Neuron fibers of the hair cells showed significant loss 7 days after the drug administration, but the number of spiral ganglia did not decrease and supporting cells showed no signs of injury. Our study suggest that combined administration of fu- rosemide and kanamycin has an synergistic ototoxic effect, and can result in hair cell loss and hearing loss in rats.

关键词： Kanamycin Furosemide Deafness model Hair cell injury, rat

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Inflammasome activation in mouse inner ear in response to MCMV induced hearing loss

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Journal of Otology 2015年第4期10卷 143-149页

作者： Xi Shi Yanfen Dong Ya Li ZenLu Zhao Huan Li Shiwei Qiu Yaohan Li Weiwei Guo Yuehua Qiao The institute of Audiology and Speech Science of Xuzhou Medical Collage Department of otolaryngology Head&Neck Surgery Institute of Otolaryngology of PLA Chinese PLA General Hospital

Objective:To identify presence of inflammasome activated in mouse cochlea with sensorineural hearing loss (SNHL) caused by cytomegalovirus (CMV) infection. Method:MCMV was injected into the right cerebral hemisphere in neonatal BALB/c mice at 2000 pfu virus titers. Auditory brainstem responses (ABRs) were tested to evaluate hearing at 21 days. Histopathological studies were conducted to confirm localizations of MCMV infected cells in the inner ear. Expression of inflammasome related factors was assessed by immunofluorescence, Quantitative real-time PCR and Western blotting. Results:In the mouse model of CMV induced SNHL, inflammasome related kinase Caspase-1 and downstream inflammatory factor IL-1b and IL-18 were found increased and activated after CMV infection in the cochlea. These factors could further up-regulate expression of IL-6 and TNF-a. These inflammatory factors are neurotoxicity and may contribute to hearing impairment. Furthermore, we also detected significantly increased AIM2 protein that accumulated in the SGN of cochleae with CMV infection. Significance:We have shown that inflammasome as a novel inherent immunity mechanism may contribute to hearing impairment. Conclusion:Our data indicate that imflammasome assemble in mouse inner ear in response to CMV infection. We have revealed a novel pa-thology event in CMV induced SNHL involving activation of inflammasome in mouse cochlea. Additionally, we have shown that inflammasome may be a novel target for prevention and treatment of CMV related SNHL. Copyright ? 2016, The Authors. Production & hosting by Elsevier (Singapore) Pte Ltd On behalf of PLA General Hospital Department of otolaryngologyHead and Neck Surgery. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： MCMV Inflammasome Caspase-1 SNHL

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Diagnosis and Treatment of Auditory Neuropathy and Related Research

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Journal of Otology 2012年第2期7卷 86-91页

作者： JI Fei YANG Shiming Department of otolaryngology Head and Neck Surgery Chinese PLA General Hospital Chinese PLA institute of otolaryngology

Introduction Deafness is one of the most common otologic diseases and a major disease that greatly impacts the Chinese population. From the Second National Sample Survey of Disabled Persons, it is estimated that there... 详细信息

关键词： Diagnosis and Treatment of Auditory Neuropathy and Related Research ABR

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