Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as ...Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.展开更多
目的探讨听障儿童Chirp声诱发的听性脑干反应(Chirp-ABR)及听性稳态反应(ASSR)的反应阈与行为测听阈值的相关性。方法研究对象为2015年1月至2018年12月确诊的31例(60耳)感音神经性听力损失儿童,年龄2~6周岁,平均3.5±1.5岁,其中男21...目的探讨听障儿童Chirp声诱发的听性脑干反应(Chirp-ABR)及听性稳态反应(ASSR)的反应阈与行为测听阈值的相关性。方法研究对象为2015年1月至2018年12月确诊的31例(60耳)感音神经性听力损失儿童,年龄2~6周岁,平均3.5±1.5岁,其中男21例(40耳,19例双耳,2例单耳),女10例(20耳);轻中度听力损失13例,重度听力损失13例,极重度听力损失5例。对所有患儿进行Chirp-ABR、ASSR以及行为听阈检测,并分析Chirp-ABR、ASSR反应阈与行为听阈值之间的相关性。结果本组对象500、1000、2000和4000 Hz Chirp-ABR反应阈分别为56.67±20.23、59.92±20.86、65.92±20.74、71.33±21.13 dB nHL,ASSR反应阈分别为81.58±22.58、77.42±23.56、77.42±23.56、92.08±21.63 dB eHL,行为听阈分别为58.33±20.86、61.67±21.84、70.0±22.53、76.83±21.59 dB HL。500、1000、2000和4000 Hz Chirp-ABR反应阈与行为听阈值之间的相关性系数(r值)分别为0.921、0.904、0.921、0.87,ASSR反应阈与行为听阈值的相关性系数(r值)分别为0.592、0.631、0.628、0.512。结论500、1000、2000、4000 Hz各个频率Chirp-ABR与行为听阈的相关性均高于ASSR,尤其在500、2000 Hz更为显著,Chirp-ABR能更加准确的反应听障儿童的真实听力。展开更多
基金supported by the National Natural Science Foundation of China,Nos.81800919(to YX),82171140(to PW)the International Cooperation and Exchange of the National Natural Science Foundation of China,Nos.82020108008(to HS),81720108010(to SY).
文摘Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.
文摘目的探讨听障儿童Chirp声诱发的听性脑干反应(Chirp-ABR)及听性稳态反应(ASSR)的反应阈与行为测听阈值的相关性。方法研究对象为2015年1月至2018年12月确诊的31例(60耳)感音神经性听力损失儿童,年龄2~6周岁,平均3.5±1.5岁,其中男21例(40耳,19例双耳,2例单耳),女10例(20耳);轻中度听力损失13例,重度听力损失13例,极重度听力损失5例。对所有患儿进行Chirp-ABR、ASSR以及行为听阈检测,并分析Chirp-ABR、ASSR反应阈与行为听阈值之间的相关性。结果本组对象500、1000、2000和4000 Hz Chirp-ABR反应阈分别为56.67±20.23、59.92±20.86、65.92±20.74、71.33±21.13 dB nHL,ASSR反应阈分别为81.58±22.58、77.42±23.56、77.42±23.56、92.08±21.63 dB eHL,行为听阈分别为58.33±20.86、61.67±21.84、70.0±22.53、76.83±21.59 dB HL。500、1000、2000和4000 Hz Chirp-ABR反应阈与行为听阈值之间的相关性系数(r值)分别为0.921、0.904、0.921、0.87,ASSR反应阈与行为听阈值的相关性系数(r值)分别为0.592、0.631、0.628、0.512。结论500、1000、2000、4000 Hz各个频率Chirp-ABR与行为听阈的相关性均高于ASSR,尤其在500、2000 Hz更为显著,Chirp-ABR能更加准确的反应听障儿童的真实听力。
