单侧听觉剥夺对听觉发育关键期小鼠内耳的影响北大核心CSCD

目的 研究单侧听觉剥夺对听觉发育关键期小鼠内耳的影响。方法 将22只出生后12天的C57BL/6小鼠随机分为正常对照组和听觉剥夺组。对听觉剥夺组进行单侧听觉剥夺,2周后解除剥夺。对正常对照组小鼠和听觉剥夺组小鼠双耳采用听性脑干反应(ABR)评估听功能,并通过免疫荧光染色对毛细胞、带状突触、螺旋神经节进行形态学观察。统计学分析听觉剥夺组小鼠的剥夺耳、未剥夺耳和正常对照小鼠在听功能和耳蜗形态学方面的差异。结果 1)听觉剥夺2周后,听觉剥夺组的剥夺耳ABR高频阈值升高,Ⅰ波潜伏期延长,与对照组小鼠相比差异有统计学意义;2)听觉剥夺组的未剥夺耳与正常对照组间ABR阈值和Ⅰ波潜伏期差异无明显差异;3)免疫荧光染色结果示听觉剥夺耳和未剥夺耳的毛细胞形态和数量未见异常;4)和对照组相比,听觉剥夺组的剥夺耳出现了带状突触数量减少,未剥夺耳与对照组之间的带状突触数量未见统计学差异,没有出现代偿性增加。结论 单侧听觉剥夺可导致听觉发育关键期小鼠剥夺耳的听功能及带状突触异常。     

听觉剥夺效应及对听力康复的影响

对称性听力损失 (根据纯音听阈和言语识别率 )的患者如果仅单耳佩戴助听器 ,那么未助听耳的言语识别率可能在随后的时间里呈进行性的下降 ,Ｓｉｌｍａｎ(1984)将这种现象称作迟发性听觉剥夺 (ｌａｔｅ -ｏｎｓｅｔａｕｄｉｔｏｒｙｄｅｐｒｉｖａｔｉｏｎ)。他首先报道了 44例双侧中重度感音神经性聋的男性 ,单耳佩戴助听器后 4到 5年有 17例对侧耳发生显著的言语识别率下降 ,并提出这一概念 ,值得注意的是纯音听阈和言语识别阈几乎没有改变[1 ] 。此后许多研究也得出相似的结果 ,并深入探讨了它的发生机制及预防措施。 1996年 15位著名听力…     

耳蜗电刺激对听觉剥夺幼鼠学习记忆能力的实验研究

目的 建立听力障碍和耳蜗电刺激模型,探讨听力障碍及耳蜗电刺激对幼鼠认知功能的影响.方法 选用健康SD幼鼠随机分成4组:①听觉剥夺组(auditory deprivation,AD);②听觉剥夺+早期耳蜗电刺激组(early intracochlear electrical stimulation,ICES1);③听觉剥夺+晚期耳蜗电刺激组(late intracochlearelectrical stimulation,ICES2);④对照组(normal control,NC).AD组、ICES1组、ICES2组在出生后第7天开始用阿米卡星500 mg/kg.d皮下注射,直到出生后第16天.对听觉剥夺的幼鼠分别于生后3周龄(早期干预组,ICES1)和生后7周龄(晚期干预组,ICES2)进行电刺激,持续3小时/天,共1周.然后对各组进行行为学检测,并与同龄对照组比较.结果 Morris水迷宫实验结果①定位航行试验:早期耳蜗电刺激组(ICES1组)逃避潜伏期于训练后第3天及第4天逐渐达正常水平(与对照组比较,P值均＞0.05),明显短于听觉剥夺组(P值均<0.05);晚期耳蜗电刺激组(ICES2)每日逃避潜伏期虽较听觉剥夺组稍有缩短,但与正常组比较,仍明显延长(均为P<0.05).②空间探索实验:早期电刺激组幼鼠在平台象限的游泳时间明显长于听觉剥夺组,穿越平台的次数较听觉剥夺组明显增多(P<0.05),达同龄正常对照组水平.而晚期电刺激组幼鼠在平台象限的游泳时间、穿越平台的次数与听觉剥夺组比较无统计学意义(P>0.05).结论 听力丧失后学习和记忆能力受损,早期耳蜗电刺激可以改善听力障碍幼鼠的学习记忆能力.     

单侧听觉剥夺后听觉中枢的重塑研究进展

单侧听觉剥夺后,听力正常耳主导听力,随着时间的延长,这种双耳信息输入的不对称,造成听觉中枢发育不对称(偏侧性改变),涉及听觉皮层及脑干听觉核团的不同区域,引起对应听觉通路发生一系列改变,包括结构、神经递质及受体等的改变,进而改变了两侧通路兴奋与抑制的平衡,损害了两耳信号的整合处理,导致声源定位能力及言语识别率降低,甚至影响患者的认知功能。这种偏侧化的改变可能会影响后续的听觉康复,因此,明确单侧听觉剥夺之后听觉中枢重塑的机制至关重要。本文就单侧听觉剥夺后听觉中枢的重塑研究进展做一回顾。     

迟发性听觉剥夺效应及与助听器佩戴的关系

脑的认知功能依赖于外周神经系统的感觉输入，在听觉系统中，外周听器损伤可以立即导致与损伤程度密切相关的听觉功能障碍，从而严重影响言语识别能力，本文所讨论迟发性听觉剥夺效应（Late-onset anditory deprivation)与听力损失程度无关。例如，对称性听力损失患者如果单耳佩戴助听器，一段时间以后，助听耳的言语识别能力将得以改善，但这种改善并非在佩戴助听器后立即发生，因此不能简单归因于听觉放大本身，相反，非助听耳的言语识别能力却发生与听力损失无关的进一步下降，这种迟发性听觉剥夺效应源于外周信号输入改变后听觉中枢功能的改变，是使用依赖性认知功能重塑的结果，但迟发性听觉剥夺效应不会发生在双耳佩戴助听器的患者，本文对多种迟发性听觉剥夺效应的认识发展过程，可逆性以及可能的机制进行了系统回顾分析，并对迟发性听觉剥夺效应对助听器佩戴的影响，今后的研究发展方向以及其临床应用价值进行了探讨。     

听力正常儿童的听觉发育

本重点介绍听力正常儿童的听觉发育和获得性经验性在发育中的作用以及听觉感受和听觉语言感受的概念。     

两种噪声刺激对豚鼠听觉早期损伤的比较

目的比较相同强度的不同噪声刺激后豚鼠听力和耳蜗外毛细胞损伤程度。方法将19只豚鼠分为娱乐噪声组(8只)、白噪声组(7只)和正常对照组(4只),白噪声组和娱乐噪声组声刺激平均强度均为105dBSPL,5小时/天,连续给声刺激5天。各组豚鼠在给噪声前及连续给噪声刺激5天结束后进行ABR和DPOAE检测,并在测试结束后取耳蜗应用异硫氰光素标记的鬼笔环肽(phalloidin-FITC)标记表皮板和静纤毛,应用碘化丙啶(PI)标记外毛细胞核,在激光共聚焦显微镜下观察毛细胞受损情况(包括核肿胀、核固缩、核缺失)。结果白噪声组和娱乐噪声组两种噪声刺激前后豚鼠ABR阈值分别为17.5±3.80、16.88±4.03dBSPL和64.64±5.36、45.94±4.55dBSPL;两组刺激前后DPOAE幅值均有所下降(P<0.05),且白噪声组比娱乐噪声组更为明显。白噪声组可观察到大量核肿胀和核固缩的外毛细胞及核缺失的毛细胞,娱乐噪声组观察到受损外毛细胞以核固缩为主,损伤总数远远低于白噪声组。结论相同强度白噪声和娱乐噪声刺激均可造成豚鼠一定程度的听力损失,娱乐噪声刺激后外毛细胞损伤以早期病变为主,其受损程度低于白噪声组。     

C57小鼠毛细胞突触带的发育观察

目的了解C57小鼠耳蜗毛细胞突触带发育的时间特点。方法全耳蜗基底膜铺片后免疫荧光染色,共聚焦显微镜观察和记录不同发育阶段C57小鼠听觉突触前膜突触带的数目与分布。运用ABR检测听力发生的时间。结果 C57小鼠出生后0d,在内外毛细胞胞质即可观察到Ctbp2信号;出生后第3天,Ctbp2信号在毛细胞上逐渐增多;出生后第6天,Ctbp2信号在毛细胞的胞质和基底侧膜上的表达达高峰,内毛细胞(35.1±3.4)个/细胞,而外毛细胞上的增加更为显著,达(21.0±3.2)个/细胞;出生后第12、30和60天,Ctbp2信号数目趋于稳定,在内毛细胞16-20个/细胞,外毛细胞1-3个/细胞,信号的分布也逐渐聚集在毛细胞的基底侧膜上。ABR检测提示C57小鼠听觉发生的平均时间为13.2天。结论毛细胞突触带出生时即已存在,出生后逐渐发育和完善。听觉发生与突触带成熟时间上的高度吻合,表明成熟突触带的形成可能是听觉发生的前提条件之一。     

婴幼儿听觉发育延迟的听力学特征分析

目的探讨婴幼儿听觉发育延迟的听力学特点及影响因素,为鉴别听觉发育延迟与永久性聋提供科学依据。方法回顾性分析6例听觉发育延迟婴幼儿从发现听力障碍到听力转为正常的历次听力诊断情况,与同期诊断为永久性聋的婴幼儿历次听力诊断情况进行比较,分析听觉发育延迟婴幼儿的听力学特点。结果①听觉发育延迟婴幼儿在历次听力诊断中,听力逐渐好转,而永久性聋患儿听力始终无变化;②听觉发育延迟婴幼儿初次诊断为重度或极重度聋者,常同时伴有中耳病变;③听觉发育延迟婴幼儿初次诊断时双耳阈值差仅0~20 dB,而初次诊断双耳阈值差过大尤其是单耳极重度或重度聋对侧耳正常的单耳听力障碍者历次复诊患耳听力均无改善则可能为永久性聋;④早期助听干预可促进听觉发育延迟婴幼儿的听觉发育。结论听力是否随婴幼儿月龄增大而好转、初次诊断重度或极重度聋是否伴有中耳积液、初诊时双耳阈值差是否≤20 dB是鉴别婴幼儿听觉发育延迟与永久性聋的重要依据;对可能为听觉发育延迟的患儿适时进行助听干预,可促进其听觉发育。     

大鼠听觉发育中听觉敏感度及时间分辨率的变化

目的 运用听觉惊跳反射前抑制方法观察大鼠听觉系统发育过程中听觉敏感度和时间分辨率的改变及两者之间的时间相关件.方法 选用日龄为14、16、18、22、26、30、35天的新生SD大鼠各20只,各日龄大鼠分为2组,每组10只,每个日龄组的大鼠均进行听性脑干反应(ABR)测试和听觉惊跳反射前抑制测试,一组大鼠在测试时标记的...     

Effects of Early Auditory Deprivation and Stimulation on Auditory Brainstem Responses in the Rat

The purpose of this study was to investigate the effect of auditory sound deprivation or stimulation on auditory brainstem responses (ABRs) during the maturation period of the rat auditory system. At postnatal day (PND) 21, 40 newborn Norway Brown male rats were categorized into 3 groups: (i) an auditory deprivation group in which a bilateral average conductive hearing loss of 27 dB was induced; (ii) an auditory activation group exposed to 65-90 dB sound pressure level; and (iii) a control group. ABR recordings were made on PND 84. In order to compare group differences in interpeak latency (IPL), sensation level (SL), defined as stimulus intensity above threshold, was used. IPL measurements and analysis were restricted to the 20-60 dB SL range. No differences were observed in the IPLs of peaks I-IV between the three groups. Small, but not statistically significant, differences in mean estimated IPLs of peaks I-IV were shown in the ranges >50 dB SL and <25 dB SL. Possible confounding factors explaining the apparent discrepancy between these results and those of other animal studies are reviewed.     

Evaluating the Perceptual and Pathophysiological Consequences of Auditory Deprivation in Early Postnatal Life: A Comparison of Basic and Clinical Studies

Decades of clinical and basic research in visual system development have shown that degraded or imbalanced visual inputs can induce a long-lasting visual impairment called amblyopia. In the auditory domain, it is well established that inducing a conductive hearing loss (CHL) in young laboratory animals is associated with a panoply of central auditory system irregularities, ranging from cellular morphology to behavior. Human auditory deprivation, in the form of otitis media (OM), is tremendously common in young children, yet the evidence linking a history of OM to long-lasting auditory processing impairments has been equivocal for decades. Here, we review the apparent discrepancies in the clinical and basic auditory literature and provide a meta-analysis to show that the evidence for human amblyaudia, the auditory analog of amblyopia, is considerably more compelling than is generally believed. We argue that a major cause for this discrepancy is the fact that most clinical studies attempt to link central auditory deficits to a history of middle ear pathology, when the primary risk factor for brain-based developmental impairments such as amblyopia and amblyaudia is whether the afferent sensory signal is degraded during critical periods of brain development. Accordingly, clinical studies that target the subset of children with a history of OM that is also accompanied by elevated hearing thresholds consistently identify perceptual and physiological deficits that can endure for years after peripheral hearing is audiometrically normal, in keeping with the animal studies on CHL. These studies suggest that infants with OM severe enough to cause degraded afferent signal transmission (e.g., CHL) are particularly at risk to develop lasting central auditory impairments. We propose some practical guidelines to identify at-risk infants and test for the positive expression of amblyaudia in older children.     

听觉剥夺及耳蜗内电刺激幼鼠听皮层和下丘核CREB 和 NMDAR1蛋白表达变化

目的：观察耳聋幼鼠及其耳聋后单耳植入电极电刺激后幼鼠听皮层和下丘核环磷酸腺苷反应元件结合蛋白（cyclic AMP response element － binding protein ,CREB）和N －甲基－D－天冬氨酸受体－1（N －methyl－D－aspartic acid receptor one ,NMDAR1）表达水平的变化。方法将66只12天龄SD幼鼠随机分为2大组,分别为耳聋造模后4周组（33只）及耳聋造模后6周组（33只）。将耳聋造模后4周组再分为对照1组、耳聋造模后4周组（4周组）及耳聋造模后3周耳蜗内电刺激组1（刺激时间为1周,简称“电刺激1组”）,每组11只大鼠;将耳聋造模后6周组再分为对照2组、耳聋造模后6周组（6周组）及耳聋造模后5周耳蜗内电刺激组2（刺激时间为1周,简称“电刺激2组”）,每组11只大鼠;对照1、2组均正常饲养。除对照1、2组外,在其余4组幼鼠颈背部、两侧下腹部皮下注射庆大霉素（总量为350 mg／kg ）,半小时后于相同部位注射呋塞米（总量为200 mg／kg ）,两周后行ABR检测,于耳聋造模成功后第3、5周分别对电刺激1、2组的幼鼠植入电极,在耳蜗内进行电刺激,每天3小时,持续7天。于耳聋造模后4、6周分别处死4、6周组大鼠取听皮层和下丘组织,通过免疫组织化学方法,观察CREB和NMDAR1表达水平的变化。结果耳聋造模成功后幼鼠ABR阈值均大于93 dB SPL ,4周组听皮层、下丘CREB和NMDAR1的表达较对照1组增加,电刺激1组CREB和NMDAR1的表达较4周组增加。6周组听皮层和下丘CREB和NMDAR1的表达较对照2组下降,电刺激2组CREB和NMDAR1的表达较6周组增加。结论听觉剥夺可导致幼鼠听皮层和下丘CREB和NMDAR1早期表达增加而晚期表达下降。耳蜗植入电极电刺激可导致幼鼠听皮层和下丘CREB和NMDAR1的表达增加,反映这两个部位神经元的可塑性变化。     

Postnatal Development of NR2A and NR2B mRNA Expression in Rat Auditory Cortex and Thalamus

Sensory cortex in the rat undergoes rapid postnatal development, especially following the onset of sensory function during so-called "critical periods." To investigate potential mechanisms in the auditory forebrain involving different NMDA receptor subunits, we have used in situ hybridization to determine expression patterns of NR2A and NR2B mRNA at postnatal days 4, 10, 13, 18, 25, and adult. In auditory cortex, NR2A mRNA expression is initially weak but increases rapidly over ~2 weeks. NR2B mRNA levels are initially high and remain high. For both subunits, expression tends to be highest in superficial layers of the cortex (except layer 1). Expression is weaker in the auditory thalamus (medial geniculate). Initially, NR2A mRNA expression is very low, whereas NR2B mRNA expression is moderate; both levels increase over ~2 weeks. Among medial geniculate subdivisions, NR2A mRNA expression occurs preferentially in the medial division, whereas NR2B mRNA expression is strongest in the ventral division. For auditory cortex and thalamus, NR2A and NR2B mRNA expression peaks about 1 week after the onset of hearing before declining slightly into adulthood. The heterogeneous distribution of NMDAR subunit mRNA throughout development may play a role in auditory forebrain development and function.     

新霉素致发育中大鼠毛细胞损伤的电镜观察

目的应用扫描电镜研究氨基甙类抗生素导致出生后发育过程中大鼠耳蜗毛细胞的损伤病理变化。方法７天龄ＳＤ大鼠肌肉注射８０ｍｇｋｇ－１ｄ－１新霉素连续８天,停药后７天处死动物制备样本进行扫描电镜观察。结果新霉素可造成出生后发育过程中的耳蜗毛细胞严重损伤,表现为底回和钩回三排外毛细胞全部损伤缺失,损伤病变累及顶回的外毛细胞,底回和钩回的内毛细胞出现纤毛脱落和细胞损伤丢失;外毛细胞损伤缺失的部位由顶部具有微绒毛的多边形细胞取代,该细胞形态与胚胎发育早期的毛细胞相似;毛细胞损伤区域未发现再生的毛细胞。结论出生后发育过程中大鼠耳蜗毛细胞对氨基甙类抗生素的敏感性较高,表面有微绒毛的多边形细胞在毛细胞损伤区域出现提示听觉感觉上皮细胞有再生的倾向。     

The Auditory Enhancement Effect is Not Reflected in the 80-Hz Auditory Steady-State Response

The perceptual salience of a target tone presented in a multitone background is increased by the presentation of a precursor sound consisting of the multitone background alone. It has been proposed that this “enhancement” phenomenon results from an effective amplification of the neural response to the target tone. In this study, we tested this hypothesis in humans, by comparing the auditory steady-state response (ASSR) to a target tone that was enhanced by a precursor sound with the ASSR to a target tone that was not enhanced. In order to record neural responses originating in the brainstem, the ASSR was elicited by amplitude modulating the target tone at a frequency close to 80 Hz. The results did not show evidence of an amplified neural response to enhanced tones. In a control condition, we measured the ASSR to a target tone that, instead of being perceptually enhanced by a precursor sound, was acoustically increased in level. This level increase matched the magnitude of enhancement estimated psychophysically with a forward masking paradigm in a previous experimental phase. We found that the ASSR to the tone acoustically increased in level was significantly greater than the ASSR to the tone enhanced by the precursor sound. Overall, our results suggest that the enhancement effect cannot be explained by an amplified neural response at the level of the brainstem. However, an alternative possibility is that brainstem neurons with enhanced responses do not contribute to the scalp-recorded ASSR.     

生长相关蛋白-43在听觉剥夺大鼠听皮层中的表达研究

目的探索听觉系统发育和损伤后修复的神经可塑性的分子机制,探索GAP-43与幼鼠听皮层发育和可塑性的关系;方法应用免疫组织化学方法,检测正常幼鼠(3周龄、4周龄及8周龄大鼠)及耳毒性药物致聋鼠发育的不同阶段(2周2天龄大鼠氨基糖苷类抗生素致聋后5天、12天及40天,即致聋的3周龄、4周龄及8周龄大鼠)GAP-43在听皮层的阳性神经元表达变化;结果发现GAP-43在刚出生大鼠听皮层阳性神经元高表达,随发育表达逐渐降低,出生后3周(NC P3W)的大鼠听皮层平均每高倍视野阳性神经元数为111.50±4.90,出生后4周(NC P4W)为84.17±3.24,出生后8周(NC P8W)为66.67±4.17;耳蜗损伤后早期GAP-43在幼鼠听皮层的表达反应性升高;结论 GAP-43与幼鼠听皮层发育和可塑性密切相关,GAP-43可作为听皮层乃至听觉系统发育和可塑性的重要标志。