Anti-apoptotic treatment in mouse models of age-related hearing loss

Age-related hearing loss (AHL), or presbycusis, is the most common neurodegenerative disorder and top communication deficit of the aged population. Genetic predisposition is one of the major factors in the development of AHL. Generally, AHL is associated with an age-dependent loss of sensory hair cells, spiral ganglion neurons and stria vascularis cells in the inner ear. Although the mechanisms leading to genetic hearing loss are not completely understood, caspase-family proteases function as important signals in the inner ear pathology. It is now accepted that mouse models are the best tools to study the mechanism of genetic hearing loss or AHL. Here, we provide a brief review of recent studies on hearing improvement in mouse models of AHL by anti-apoptotic treatment.

Risk of Hearing Loss Caused by Multiple Acoustic Impulses in the Framework of Biovariability

We consider the hearing loss injury among subjects in a crowd with a wide spectrum of individual intrinsic injury probabilities due to biovariability. For multiple acoustic impulses, the observed injury risk of a crowd vs the effective combined dose follows the logistic dose-response relation. The injury risk of a crowd is the average fraction of injured. The injury risk was measured in experiments as follows: each subject is individually exposed to a sequence of acoustic impulses of a given intensity and the injury is recorded;results of multiple individual subjects were assembled into data sets to mimic the response of a crowd. The effective combined dose was adjusted by varying the number of impulses in the sequence. The most prominent feature observed in experiments is that the injury risk of the crowd caused by multiple impulses is significantly less than the value predicted based on assumption that all impulses act independently in causing injury and all subjects in the crowd are statistically identical. Previously, in the case where all subjects are statistically identical (i.e., no biovariability), we interpreted the observed injury risk caused by multiple impulses in terms of the immunity effects of preceding impulses on subsequent impulses. In this study, we focus on the case where all sound exposure events act independently in causing injury regardless of whether one is preceded by another (i.e., no immunity effect). Instead, we explore the possibility of interpreting the observed logistic dose-response relation in the framework of biovariability of the crowd. Here biovariability means that subjects in the crowd have their own individual injury probabilities. That is, some subjects are biologically less or more susceptible to hearing loss injury than others. We derive analytically the distribution of individual injury probability that produces the observed logistic dose-response relation. For several parameter values, we prove that the derived distribution is mathematically a proper density function. We further study the asymptotic approximations for the density function and discuss their significance in practical numerical computation with finite precision arithmetic. Our mathematical analysis implies that the observed logistic dose-response relation can be theoretically explained in the framework of biovariability in the absence of immunity effect.

Auditory characteristics of noise-exposed memberscrossing age-related groups

Objective： To report audiological characteristics in a group of noise-exposed crew members on board ships. Methods and materials： Clinical and audiological measurements including pure-tone thresholds, acoustic immittance results and tinnitus questionnaires were collected from both the ship crew members （study subjects） and their land based colleagues （controls）. Results： 1） Noise exposed crew members showed not only high frequency, but also low frequency hearing loss; 2） Hearing impairment increased with age, with 65.5% of crew members younger than 50 years showing normal hearing while only 14.9% of those older than 50 years had normal hearing; 3） hearing loss gradually increased with the extension of on board career time; and 4） Most study subjects reported high pitch tinnitus, significantly more than the control group although not significantly different among different age groups. Conclusion： Noise induced hearing impairment from working on board ships shows specific frequency and age characteristics. Understanding these characteristics is important for advancing relevant studies and for effective prevention of noise-induced hearing loss in ship crew members.

Risk of Hearing Loss Injury Caused by Multiple Flash Bangs on a Crowd

A flash bang is a non-lethal explosive device that delivers intensely loud bangs and bright lights to suppress potentially dangerous targets. It is usually used in crowd control, hostage rescue and numerous other missions. We construct a model for assessing quantitatively the risk of hearing loss injury caused by multiple flash bangs. The model provides a computational framework for incorporating the effects of the key factors defining the situation and for testing various sub-models for these factors. The proposed model includes 1) uncertainty in the burst point of flash bang mortar, 2) randomness in the dispersion of multiple submunitions after the flash bang mortar burst, 3) decay of acoustic impulse from a single submunition to an individual subject along the ground surface, 4) the effective combined sound exposure level on an individual subject caused by multiple submunitions at various distances from the subject, and 5) randomness in the spatial distribution of subjects in the crowd. With the mathematical model formulated, we seek to characterize the overall effect of flash bang mortar in the form of an effective injury area. We carry out simulations to study the effects of uncertainty and randomness on the risk of hearing loss injury of the crowd. The proposed framework serves as a starting point for a comprehensive assessment of hearing loss injury risk, taking into consideration all realistic and relevant features of flash bang mortar. It also provides a platform for testing and updating component models.

Prevention of Hearing Loss by Alteration of the Systemic Immune System

Although congenital sensorineural hearing loss (SHL) in the bilateral cochleae mainly results from genetic abnormalities, chronic SHL progressing in later life is often influenced by systemic immune disturbances, including autoimmunity, chronic inflammation, and immunosenescence. We have investigated the relationship between the inner ear and systemic immunity and reviewed the possibilities to prevent SHL, including autoimmune SHL and age-related SHL. We also demonstrated two lymphocyte populations, interleukin 1 receptor type II (IL-1R2)-positive T cells (T1R2) and naturally occurring regulatory T cells (nTregs) in CD4+ T cells, which increase with aging, suppress host immune function and promote organ degeneration. Alterations in systemic immunity by fewer microbial antigen challenges in the living environment, elimination of immune suppressive lymphocytes, or immune rejuvenation with a reconstituted thymus may contribute not only to renew the cochlear function in SHL, but also to extend the healthy life of functional organs in a vigorous and youthful body, one of humanity’s greatest dreams.

老年性聋患者人工耳蜗植入效果分析

目的 探究老年性聋患者人工耳蜗植入术后听觉言语康复效果及生活质量的变化。方法 对31例行人工耳蜗植入的老年性聋患者进行听力学、言语功能及生活质量评估并比较差异。听力学评估采用助听听阈,言语能力评估采用词表识别率,评估时间为术前、开机后6个月及开机后12个月。生活质量评估采用Nijmegen人工耳蜗植入量表(NCIQ),评估时间为术前及开机后12个月。结果 共纳入31例患者,31例患者术前、开机后6个月及开机后12个月助听听阈分别为(62.55±3.69)、(46.58±5.14)、(38.68±4.26)dBHL,差异具有统计学意义(P<0.05)。术前、开机后6个月及开机后12个月单音节词识别率分别为(9.55±5.81)%、(54.77±8.90)%、(68.52±7.21)%,差异具有统计学意义(P<0.05);术前、开机后6个月及开机后12个月双音节词识别率分别为(19.87±9.72)%、(64.00±6.53)%、(74.26±6.79)%,差异具有统计学意义(P<0.05);术前、开机后6个月及开机后12个月短句识别率分别为(28.00±10.58)%、(68.52±7.78)%、(77.61±8.59)%,差异具有统计学意义(P<0.05)。术前及开机12个月NCIQ总量表得分分别为(35.90±5.80)、(65.16±8.18)分,差异具有统计学意义(P<0.05)。结论 人工耳蜗植入可以改善老年性聋患者的听觉言语能力及生活质量,对于重度以上听力损失且助听器效果不佳的老年性聋患者可以选择人工耳蜗植入。

年龄相关性听力损失大鼠耳蜗代谢组学的初步研究

目的应用大鼠耳蜗代谢组学技术探索年龄相关性听力损失的发生机制。方法选择2月龄(年轻组)和14月龄(老年组)SD大鼠各15只,通过听性脑干反应(ABR)检测各组大鼠听觉功能;利用HE染色观察两组耳蜗组织形态,并通过流式细胞术检测耳蜗组织氧化应激状态。每组选取5只采用非靶向超高效液相色谱-串联质谱(LC-MS/MS)技术对耳蜗组织进行代谢组学检测,分析衰老耳蜗代谢差异。结果相较于年轻大鼠,老年大鼠ABR检测8、16、32 kHz纯音及click声反应阈值显著升高(P<0.05),HE染色显示耳蜗衰老相关血管纹萎缩(P<0.05),流式细胞术检测提示氧化应激水平明显升高(P<0.05)。代谢组学检测老年组耳蜗中共鉴定出124种差异代谢物,其中包括鞘氨醇、全反式维生素甲酸、油酰胺在内的16种代谢物显著上调,而嘌呤、牛磺酸、硫胺素、脯氨酸及其衍生物等108种代谢物水平明显降低;提示蛋白质合成与分解、鞘脂代谢、嘌呤代谢、氧化应激相关信号转导、细胞死亡、辅酶生物合成等生理病理机制可能与耳蜗衰老有关。结论细胞衰老和耳蜗代谢功能失调可能是导致年龄相关性听力损失的重要机制。

年龄相关性听力损失健康危害与日常干预的研究进展

年龄相关性听力损失(ARHL)是当前老龄化社会中最普遍且严重威胁老年人身心健康的慢性疾病,其是一种以听觉毛细胞丢失、血管纹病变、螺旋神经节凋亡以及听觉神经中枢退化为主要表现的感音神经性听力损失,显著降低患者的生活质量。本文重点对ARHL与阿尔茨海默病、抑郁症、虚弱之间的关系以及ARHL日常干预的研究进展进行综述,旨在提高人们对ARHL健康危害的认知水平和重视程度,并通过实施日常干预措施形成健康的生活方式来延缓ARHL的发生及发展。

老年性聋和认知功能障碍的研究进展

随着老年人年龄的增长,听力损失的患病率逐渐增加,是影响老年人身心健康、认知功能、社会独立性和生活质量的重要因素,严重者可导致痴呆和阿尔茨海默病的早期标志性症状。我们主要就老年性聋与认知功能障碍的相关性及研究进展进行阐述。

老年性聋发病机制研究进展

老年性聋是以隐匿性、缓慢进行性双侧感音神经性听力下降为特征的疾病,其发生和发展是一个多因素作用的过程,每种因素的作用在个体间差异较大。针对老年性聋的发病机制,目前已有一定研究,主要可分为离子通道异常、耳蜗突触病变、活性氧自由基、激素作用、线粒体异常、遗传因素等诸多方面,本文对近年来老年性聋发病机制进行总结。

局部麻醉下人工耳蜗植入手术的初步探索

人工耳蜗植入(CI)手术已成为重度-极重度老年性听力损失患者听力言语康复的重要手段。老年人群常合并有多种基础疾病而无法耐受全麻操作,本研究旨在通过1例局麻人工耳蜗植入手术的实施、残余听力的保留,探索局部麻醉在老年性听力损失人工耳蜗植入手术中的可行性。

年龄相关性听力损失的表观遗传学研究进展

人体随着年龄增长会出现一系列衰老现象,临床上将老年开始出现进行性的、对称性的感音神经性听力损失称为年龄相关性听力损失(age-related hearing loss, ARHL)。ARHL发病机制复杂,遗传易感因素是ARHL的重要因素之一,其中表观遗传学,如DNA甲基化、非编码RNA调控和组蛋白修饰对ARHL的发生发展有密切关系。我们综述了近年来与ARHL相关的表观遗传学研究进展,旨在为ARHL的预防及治疗提供帮助。

年龄相关性听力损失与营养的关系

年龄相关性听力损失是老年人群中常见的慢性疾病,其防治问题受到医学界的高度重视。合理的膳食调整能明显地延缓听力衰退,并降低年龄相关性听力损失的发病率。本文旨在探讨年龄相关性听力损失的成因,深入研究营养素与年龄相关性听力损失之间的关系及作用机制,提出科学的饮食建议,为预防和治疗年龄相关性听力损失提供思路。

老年人年龄相关性听力损失的研究进展

年龄相关性听力损失(ARHL)是随年龄增长而出现的缓慢进行性感音神经性听力减退。双侧听力损失程度可能不一致,带来诸多的负面情绪,严重影响患者的生活质量。本文对ARHL的病因、影响因素、不良影响和康复治疗方法进行综述,提出展望,为开展该病的临床和基础研究提供建议,为医护人员提供对ARHL的认识及制订干预和康复措施提供参考依据,从而提升老年人的生活质量。

当归芍药散调控IKK/IκBα/NF-κB通路对老年性聋小鼠耳蜗螺旋神经节细胞凋亡的影响

目的探究当归芍药散调控核转录因子-κB抑制蛋白激酶(IKK)/核因子κB抑制蛋白(IκBα)/核因子-κB(NF-κB)通路对老年性聋小鼠耳蜗螺旋神经节细胞凋亡的影响。方法将48只C57BL/6J小鼠随机分为老年性聋模型组(Model组)、低剂量当归芍药散组(中药-L组,3.2 g/kg生药)、高剂量当归芍药散组(中药-H组,6.4 g/kg生药)和高剂量当归芍药散+IKK/IκBα/NF-κB信号通路激活剂白藜芦醇(RES)组(中药-H+RES组,6.4 g/kg生药+43.33 mg/kg RES),每组12只小鼠;取12只2月龄的C57BL/6J小鼠作为对照组(Control组)。采用听性脑干反应(ABR)检测各组小鼠听阈值;HE染色观察小鼠耳蜗螺旋神经节的病理变化,并对小鼠耳蜗中回与底回的螺旋神经节细胞的数量进行计数;TUNEL染色法检测小鼠耳蜗螺旋神经节细胞的凋亡。ELISA法检测小鼠耳蜗组织中丙二醛(MDA)与超氧化物歧化酶(SOD)水平。qRT-PCR法检测小鼠耳蜗组织中IL-1β、IL-6与TNF-αmRNA水平。Western blot法检测小鼠耳蜗组织IKK/IκBα/NF-κB通路与凋亡相关蛋白的表达。结果Model组小鼠较Control组小鼠8 kHz、16 kHz、24 kH、32 kHz听阈值、耳蜗螺旋神经节组织TUNEL阳性细胞数、耳蜗组织MDA及IL-1β、IL-6与TNF-αmRNA水平、p-IκBα、凋亡蛋白(Bax、cleaved-Caspase-3)表达水平、IKK、NF-κB p65磷酸化水平均显著升高(均P<0.05),耳蜗螺旋神经节细胞数量、SOD水平、IκBα蛋白表达水平显著降低(均P<0.05),耳蜗螺旋神经节细胞的形态异常、排列疏松紊乱,发生空泡化,出现病理学损伤。中药-L组、中药-H组小鼠较Model组相应指标变化程度较轻(均P<0.05)。RES减弱了当归芍药散对老年性聋小鼠耳蜗螺旋神经节细胞凋亡的抑制作用。结论当归芍药散可能通过下调IKK/IκBα/NF-κB通路抑制老年性聋小鼠耳蜗螺旋神经节细胞凋亡。

Correlation of PDCD5 and Apoptosis in Hair Cells and Spiral Ganglion Neurons of Different Age of C57BL/6J Mice

This study examined the expression pattern of programmed cell death 5 (PDCD5) in co-chlear hair cells and spiral ganglion neurons (SGNs) and its association with age-related hearing loss in mice.Sixty C57BL/6J (C57) mice at different ages were divided into four groups (3,6,9 or 12 months).PDCD5 expression was detected by using immunohistochemistry,real-time PCR and Western blot.Morphological change of the cochleae was also evaluated by using immunoassay.The results showed that the expression of PDCD5 had a gradual increase with ageing in both protein and RNA levels in C57 mice,as well as gradually increased apoptosis of cochlear hair cells and SGNs.In addition,we also found that caspase-3 activity was enhanced and its expression was enhanced with ageing.It is implied that overexpression of PDCD5 causes the increase in caspase-3 activity and the subsequent increase of apoptosis in cochlear hair cells and SGNs,and thereby plays a role in the pathogenesis of presbycusis.Thus,PDCD5 may be a new target site for the treatment and prevention of age-related hearing loss.

年龄相关性听力损失相关信号通路研究进展

年龄相关性听力损失(age-related hearing loss,ARHL)又称老年性聋(presbycusis),是一种在老年人中普遍存在的慢性疾病,其主要表现为进行性听力下降。氧化应激、细胞凋亡及线粒体功能异常等机制在ARHL发展进程中起重要作用,而其相关信号通路在其中也发挥重要作用。本文对目前研究较多的ARHL相关信号通路进行综述,旨在为进一步探讨ARHL的发病机制提供参考,为寻找新的治疗靶点提供新思路。

基于VOSviewer的年龄相关性听力损失研究文献计量分析

目的了解年龄相关性听力损失研究现状、研究热点及其趋势,为进一步研究年龄相关性听力损失提供有效的理论依据。方法选取CNKI数据库和WOS数据库时间跨度为1992-2022年符合纳入/排除标准的文献,使用VOSviewer软件进行可视化分析。结果国内外发文量整体呈上升趋势。WOS数据库发文量较CNKI数据库增长相对较快。发表期刊主要分布于听力学、耳鼻咽喉头颈外科学、老年科学、神经科学等相关领域。研究热点以年龄相关性听力损失、听力损失、老年人、助听器、耳蜗为主。结论ARHL研究在发文数量方面国内外基本保持一致。其在临床研究和基础研究虽然侧重比重不同,但整体方向均以纵向深入为主。各研究团队间进行多中心、多学科、多领域合作成为一种必然趋势,为进一步探索ARHL内在机制和构建科学有效的诊疗思路和方法提供理论依据。

老年性聋患者复杂听觉场景事件相关电位的特征研究

目的研究老年性聋患者复杂听觉环境下事件相关电位(event related potential,ERP)的特征及其与认知能力及言语辨别能力的相关性,了解其言语辨别能力下降相关的中枢处理过程。方法采集25名老年性聋患者和25名听力正常年轻人的“鸡尾酒会”场景下ERP数据,比较相关成分振幅、峰值潜伏期及脑区激活差异。同时对老年性聋患者进行认知能力评估,并对其中14名老年人进行言语辨别能力测试,分析其与ERP相关性。结果老年性聋患者与年轻人相比关联性负变(contingent negative variation,CNV)振幅降低(F=5.174,P=0.027),同时N1、P1成分潜伏期延长(N1:F=6.067,P=0.021;P1:F=13.985,P=0.001),N1振幅升高(F=4.301,P=0.049)。单声源情况下老年性聋组枕叶激活减弱(t=-4.396,P<0.001),多声源情况下减弱进一步扩大到颞叶皮质(t=-5.569,P<0.001)。老年性聋组中,随年龄增长,CNV振幅下降(r=-0.460,P=0.021),P1潜伏期延长(r=0.419,P=0.037),TCT与CNV振幅呈正相关(r=0.601,P=0.023),认知量表总分与N1振幅呈负相关(r=-0.643,P=0.002)。结论老年性聋患者注意力资源分配与预期准备能力较年轻人显著下降,在单声源情况下出现选择性注意和工作记忆能力下降,多声源情况下进一步表现出显著的听觉皮层激活不足。注意力资源分配能力与总体认知水平相关,并随年龄增加而衰退,参与了老年性聋患者言语辨别能力下降的过程。

老年性耳聋病因及分子机制的研究进展

老年性耳聋是老年人群中最常见的感觉缺陷之一,又称为年龄相关性听力损失,是老年人最普遍的感觉缺陷。随着社会逐渐老龄化,老年性耳聋的发病率越来越高。老年性耳聋严重影响了老年人的身心健康,导致老年人的生活质量下降、认知能力改变、社交孤立以及抑郁、沟通障碍等。研究其病因及发病机制对老年性耳聋的诊断、治疗和预防具有重要意义。本综述总结了老年性耳聋分子机制、致病因素、病理分型、治疗手段等。