外周听觉改变致听皮质突触N-甲基D-天冬氨酸受体亚基表达变化

目的观察听觉剥夺后重塑模型中听皮质突触N-甲基D-天冬氨酸受体亚基(N-methyl-D-aspartate receptor subunit 2B,NR2B)表达变化。方法采用清洁级SD大鼠90只,分成听觉剥夺组、听觉剥夺后重塑组及对照组,Optiprep沉降梯度超速离心从初级听皮质提取高度纯化的突触体后,采用Western blotting蛋白质印迹检测技术对生后听觉剥夺14天组、28天组、42天组、听觉剥夺7天后再给予纯声暴露的各实验组听皮质突触体NR2B表达进行比较。结果听觉剥夺使生后14天组和28天组动物听皮层NR2B表达水平明显下降(P<0.05),听觉剥夺7天后再给予纯声暴露则又使NR2B表达水平明显提高(P<0.05),呈现双向调节趋势。听觉剥夺和纯声暴露对生后42天组成熟大鼠听皮层NR2B表达不再产生明显调节作用(P>0.05)。结论在大鼠生后发育关键期,听觉剥夺、可改变听皮层NMDA受体NR2B蛋白表达水平;为研究感觉功能发育可塑性机制提供了重要实验资料。     

耳鸣大鼠NMDA受体亚型1、2A、2B的表达研究

目的研究耳鸣大鼠听皮层NMDA（N-甲基-D-天冬氨酸,N-methyl-D-aspartate）受体亚型1、2A、2B（NR1、NR2A、NR2B）的表达变化,从而推测其在耳鸣的发生中可能的作用机制。方法按照随机化原则将动物分成3组,每组9只：A组为耳鸣模型组、B组为生理盐水组、C组为空白对照组。A组通过腹腔注射水杨酸钠并用食物抑制法进行验证。造模成功后运用核酸荧光染料SYBR Green实时荧光定量PCR（Polymerase Chain Reaction,聚合酶链反应）方法检测NMDA受体三种亚型的表达情况。结果NR1在A组的表达显著低于C组（P〈0.05）,NR2A在A组的表达则显著高于C组（P〈0.05）,而A、C两组之间NR2B的表达差异比较无统计学意义（P〉0.05）。NMDA受体三种亚型B、C两组之间表达差异比较均无统计学意义（P〉0.05）。A组NR2A、NR2B与NR1表达量的比值较C组均增大。结论耳鸣大鼠听皮层NMDA受体调节亚基的调控作用增大,突触局部受体蛋白质合成改变,听皮层发生了与NMDA受体相关的可塑性变化,这可能是耳鸣产生的机制之一。     

外周听觉活性改变诱导在体听皮层突触NMDA受体表达变化

目的 观察听觉剥夺和耳蜗电刺激对听皮质突触N-甲基-D-天冬氨酸受体(N-methyl-D-as-partate receptor，NMDAR)表达的影响。方法 经两次不连续梯度超速离心，从初级听皮质提取高度纯化的突触体后，采用Western blotting对耳毒性聋组、听力正常组及电耳蜗内刺激0.5～2h的各实验组听皮质突触体NMDAR三个亚型的表达进行比较。结果 证实了听觉剥夺的成年或发育期大鼠耳蜗电刺激仅仅1.5小时可以诱导突触体NR2A蛋白的显著增加，但NR1和NR2B蛋白量的改变并不显著。结论 在体大鼠的听皮质存在活性依赖的突触的NR2A蛋白的表达。     

c-fos及NR2A在耳鸣大鼠听皮层中的表达

目的通过检测神经元功能可塑性标记物快反应基因c-fos和N-甲基-D-天门冬氨酸受体（N-methyl-D-aspartate receptor,NMDAR）亚型NR2A在耳鸣大鼠听皮层中的表达探讨听皮层的可塑性变化及其在耳鸣产生中所起的作用.方法将30只白色Wistar大鼠随机分为3组,耳鸣模型组（12只）、生理盐水组（12只）和空白对照组（6只）.注射水杨酸钠造模并用行为学方法证实动物感受到耳鸣后,利用免疫组化技术检测动物听皮层中c-fos和NR2A的表达,并用数字图像分析系统进行分析.结果12只注射水杨酸钠的耳鸣模型组大鼠全部造模成功.c-fos基因的表达产物FOS蛋白主要存在于皮层神经元的胞核,其阳性细胞的数量及所占面积的百分比在耳鸣组显著高于对照组（P值均＜0.01）;NR2A受体主要表达在锥形细胞的胞膜上,其阳性细胞的数量、染色强度和面积百分比均显著强于对照组（P值均＜0.01）.结论耳鸣大鼠听皮层中c-fos和NR2A的表达明显增多,一方面表明神经递质及受体可能参与了耳鸣的发生;另一方面提示耳鸣大鼠听皮层中发生了功能可塑性改变,这种改变可能在耳鸣的发生发展中起重要作用.     

水杨酸盐对大鼠听觉中枢超微结构影响的初步研究

目的　腹腔长期注射水杨酸盐后,检测大鼠听皮层和下丘的突触超微结构改变。方法　大鼠分为正常对照组、急性注射组、慢性注射组和慢性恢复组共4个组,取材行透射电镜检测听皮层、下丘和小脑的突触超微结构变化,观察各组间的差异。结果　与正常对照组比较,慢性注射组出现突触前囊泡增多（t 下丘=-4.61,t 听皮层=-7.00,P 均＜0.01）、突触后致密区增厚（t 下丘=-4.72,P＜0.01;t 听皮层=-3.15,P＜0.05）、突触曲率上升（t 下丘=-2.32,t 听皮层=-3.17,P 均＜0.05）以及突触活性区长度增加（t 下丘=- 4.89,t 听皮层=-3.48,P 均＜0.01）,急性注射组仅出现突触前囊泡的大量释放（t 下丘=-10.57,t 听皮层=-8.34,t 小脑=-9.18,P 均＜0.01）。慢性恢复组与正常对照组比较未出现显著性差异（P＞0.05）。结论　慢性腹腔注射水杨酸后,大鼠下丘和听皮层出现突触神经递质释放增多和传递效率上升的改变。在中枢可塑性的调控下,长期应用水杨酸盐使听觉中枢不断发生结构和功能变化。     

感音神经性聋患者听觉皮层BOLD-fMRI研究

目的利用血氧水平依赖的功能磁共振成像（blood oxygenation level dependent functional magnetic resonance imaging,BOLD—fMRI）技术观察感音神经性聋患者纯音刺激时大脑听觉皮层激活情况,探讨感音神经性聋的中枢客观检查方法。方法对22例单侧中重度感音神经性聋患者（耳聋组）和15例健康志愿者（对照组）行听觉刺激BOLD-fMRI检查,比较两组纯音刺激时听觉皮层激活的体积和信号强度。结果对照组纯音刺激单耳时,对侧听觉皮层激活体积和信号强度明显大于同侧（P〈0．01）,表现为对侧半球传导优势;耳聋组刺激健侧时健侧听觉皮层激活体积和信号强度大于患侧,但差异无统计学意义（P〉0．05）。结论感音神经性聋患者纯音刺激健耳时对侧听觉半球传导优势消失,其听觉皮层可能发生了结构重塑。     

慢性噪声暴露对大鼠听皮层及海马脑区胰岛素样生长因子－1表达的影响

目的：观察慢性噪声暴露后大鼠听皮层及海马脑区胰岛素样生长因子－1（insulin－like growth fac-tor－1,IGF－1）的表达,探讨其在长期噪声性中枢神经系统损伤中的作用。方法成年健康雄性 Wistar 大鼠16只,随机分为噪声组和对照组各8只,噪声组暴露于100 dB SPL 白噪声28天,每天4小时,制成慢性噪声暴露模型,对照组不予任何处理。造模结束后检测两组大鼠 ABR 反应阈,并采用免疫组织化学染色方法检测 IGF－1在听皮层和海马的表达。结果噪声组造模结束后 ABR 反应阈（80．62±4．58 dB SPL）较对照组（38．75±3．54 dB SPL）明显升高（P＜0．05）,听皮层及海马脑区 IGF－1阳性神经元数目和表达强度均较对照组显著增加（P＜0．05）。结论慢性噪声暴露可以使听皮层及边缘系统海马脑区 IGF－1表达增高,这可能与其对中枢神经系统噪声性损伤的保护作用有关。     

原发性高血压患者听觉功能早期损害的临床研究

目的：探讨高血压对听觉功能早期损害的听力学特征,为临床研究和防治耳聋提供参考。方法：将68例（136耳）原发性高血压患者分为无眼底动脉硬化的高血压A组35例（70耳）,及伴有眼底动脉硬化的高血压B组33例（66耳）;另选30例（60耳）年龄、性别匹配且无高血压,听力正常者为对照组,分别进行纯音听阈、畸变产物耳声发射（DPOAE）等听力学测试。结果 高血压B组2000～8000Hz纯音听阈提高（P〈0．05）,高血压A组的纯音听阈与对照组比较差异均无统计学意义（P〉0．05）;高血压A、B组的DPOAE反应幅值下降（P〈0．01）,仅高血压B组4000Hz的DPOAE检出率下降（P〈0．05）。结论：高血压会影响患者的听觉系统,即使患者主观上无明显的听力下降,但听觉功能可能已出现早期改变。     

双侧耳蜗毁损后大鼠听皮层突触素表达的变化

目的观察双侧耳蜗毁损后大鼠听皮层(auditory cortex,AC)突触素表达水平的变化。方法30只SD大鼠随机均分为6组:双侧耳蜗毁损后3、7、14、21、30天组及假手术对照组,每组各5只。双侧耳蜗毁损后不同时间行听皮层突触素二步法免疫组化染色,观察突触素表达的变化。结果双侧耳蜗毁损后3天突触素表达增高,毁损后7天突触素表达较毁损后3天有所下降,毁损后14、21天突触素表达持续上升,21天时上升到最高峰,毁损后30天突触素表达开始下降,除毁损后7天组外,其余各组与假手术对照组差异均有统计学意义。各组左右耳表达差异均无统计学意义。结论大鼠双侧耳蜗去传入损伤后,突触素表达的动态变化反映了听皮层内神经元突触的重塑情况。     

大鼠听皮层发育关键期胶质纤维酸性蛋白表达及听功能变化

目的：观察大鼠听觉发育关键期听功能的变化及听皮层星形胶质细胞标记物胶质纤维酸性蛋白（glial fibrillary acidic protein ,GFAP）的表达。方法清洁级 SD 大鼠幼鼠50只随机分成出生后第14、21、28、35和42天组,每组10只,分别检测各组大鼠 ABR 反应阈后,采用免疫组化染色方法及 Western blot 检测各组大鼠听皮层 GFAP 的表达。结果大鼠出生后第14、21、28、35、42天组 ABR 平均反应阈分别为84．5±4．97、70．5±3．69、58．5±5．80、37．0±4．83和35．5±3．69 dB SPL,除第35天组与第42天组之外,其余各组两两之间比较差异均有统计学意义（P＜0．05或 P＜0．01）;第14、21、28、35、42天组大鼠听皮层 GFAP 平均累积光密度值（IOD）分别为474．36±234．56、1465．93±474．96、2163．06±353．36、6572．01±808．88和7244．37±932．90,各组间两两相比差异均有显著统计学意义（P＜0．05或 P＜0．01）。第14、21、28、35和42天组大鼠听皮层 GFAP 蛋白表达水平分别为1．00±0．06、3．07±0．07、4．92±0．05、6．88±0．03和8．92±0．04,各组间两两相比差异有统计学意义（P＜0．05）。结论大鼠出生后第14～42天其 ABR 反应阈逐渐下降,GFAP 表达逐渐增强,提示星形胶质细胞可能有促进听皮层及听觉中枢的发育与成熟的作用。     

听神经病的听功能状态分析

目的 :探讨听神经病的听功能状态及病损部位。方法 :分析 6 5例听神经病患者的临床资料、纯音测听、声导抗测试、听性脑干反应 (ABR)、4 0Hz听觉相关电位及OAE检查结果。结果 :听神经病的低频听力损失源于蜗后的传入、传出神经及听性脑干受损 ,表现为声反射、传出抑制、ABR异常及诱发性OAE与纯音听阈不呈平行关系 ,与之相对应 ,低频区的外毛细胞处于失抑制的超常活动状态 ,表现为低频区SOAE增强、TEOAE反应幅值及DPOAE幅值升高 ;听神经病的高频听力损失源于耳蜗的外毛细胞损害 ,表现为高频区DPOAE幅值与纯音听阈呈一致性下降 ;听神经病的中频听力损失最轻或接近正常 ,表现为 2kHz附近的纯音听阈和DPOAE幅值均接近于正常。结论 :听神经病的传入、传出系统及耳蜗水平均有不同程度的功能障碍 ,其病损部位主要在耳蜗传入、传出神经 ,向上可侵及脑干 ,向下可侵及耳蜗     

Risk factors for auditory neuropathy/auditory synaptopathy

AIMS: It was the aim of this study to describe risk factors in auditory neuropathy/auditory synaptopathy (AN/AS). METHODS: Between 1997 and 2005, we diagnosed 37 children with AN/AS. They underwent a critical chart review for risk factors and etiological coincidences in this idiosyncratic disorder. RESULTS: Eighteen neonates had a history of prematurity and low birth weight. Hyperbilirubinaemia was present in 13 children. Three patients had evidence of infection during pregnancy, and AN/AS was associated with complex syndromal diseases in 2 cases. A congenital, familial pattern was seen in 2 siblings. Seven patients had idiopathic AN/AS. CONCLUSION: Rather than being a single etiological entity, AN/AS comprises a spectrum of risk factors and associated problems affecting the cochlea and the auditory pathway. This study shows that the majority of AN/AS in children is the result of perinatal problems and is not genetic in origin. Hyperbilirubinaemia is a common and etiologically significant finding in infants suffering from AN/AS. Thus, early hearing screening for AN/AS including transient evoked otoacoustic emissions and auditory brainstem response assessment among neonates with risk factors for AN/AS is crucial in order to better manage patients suffering from this disorder.     

听神经病/听觉失同步化患者的交替短声诱发耳蜗电图

目的 分析听神经病/听觉失同步化(auditory neuropathy/auditory desynchronization.AN/AD)患者交替短声诱发的耳蜗电图特征,探索耳蜗电图在确定听神经病,听觉失同步化病变部位时的应用价值.方法 AN/AD组患者14人,共28耳,所有患者听性脑干反应(ABR)波形缺失或严重分化异常,耳声发射正常:听力正常对照组28人,共35耳.对两组受试者行耳蜗电图(ECochG)检查,使用交替极性短声作为刺激信号.观测AN/AD组和对照组ECochG的波形,并对比:(1)CAP-N1(复合动作电位N1波)的峰潜伏期;(2)-SP(总和电位)和CAP绝对幅度;(3)-SP和CAP幅度比值;(4)CAP反应周值.结果 对照组全部引出分化良好的CAP和-SP.AN/AD组ECochG波形可分为四种类型:(1)可同时引出-SP、CAP,占60.7%;(2)仅有-SP引出,未见CAP引出,占10.7%;(3)仅有CAP引出,占3.6%;(4)-SP、CAP均未引出,占25%.AN/AD组与对照组的CAP潜伏期(P=0.052)无统计学差异;ANIAD组的CAP绝对幅度低于对照组(P<0.001),-SP(P=0.045)绝对幅度、-SP/CAP幅度比(P<0.001)和阈值(P<0.001)高于对照组.结论 在ABR引不出或分化较差时,耳蜗电图是一种比较可靠的评估外周听觉神经功能的方法,在AN/AD的诊断中能够发挥重要作用.     

The auditory characteristics of children with inner auditory canal stenosis

Conclusions This study shows that the prevalence of auditory neuropathy spectrum disorder (ANSD) in the children with inner auditory canal (IAC) stenosis is much higher than those without IAC stenosis, regardless of whether they have other inner ear anomalies. In addition, the auditory characteristics of ANSD with IAC stenosis are significantly different from those of ANSD without any middle and inner ear malformations. Objectives To describe the auditory characteristics in children with IAC stenosis as well as to examine whether the narrow inner auditory canal is associated with ANSD. Method A total of 21 children, with inner auditory canal stenosis, participated in this study. A series of auditory tests were measured. Meanwhile, a comparative study was conducted on the auditory characteristics of ANSD, based on whether the children were associated with isolated IAC stenosis. Results Wave V in the ABR was not observed in all the patients, while cochlear microphonic (CM) response was detected in 81.1% ears with stenotic IAC. Sixteen of 19 (84.2%) ears with isolated IAC stenosis had CM response present on auditory brainstem responses (ABR) waveforms. There was no significant difference in ANSD characteristics between the children with and without isolated IAC stenosis.     

Role of auditory stimulation in maturation of the auditory pathway

OBJECTIVE: To compare the maturation of the auditory pathway, as shown by electrical brainstem auditory potentials (EABRs), in ears with and without prior auditory stimulation. MATERIAL AND METHODS: Electrophysiological data were collected prospectively from ears which had received cochlear implants. Implant-evoked (Imp)EABRs were recorded. Thirty children, implanted after January 2000, were selected according to a strict inclusion/exclusion protocol. All the children had received a 22-channel Nucleus cochlear implant (CI24 series). Intraoperatively, ImpEABRs were recorded using the Medelec Synergy Evoked Response system in conjunction with Nucleus Neural Response Telemetry software. The ImpEABR latencies of waves eII, eIII and eV and the morphology of wave eV were assessed. RESULTS: ImpEABRs alter during the first 12 months of life. The latency becomes shorter during this period and the morphology of wave eV alters from a broad shape to a more distinct waveform. This appears to occur independently, even in the absence of auditory stimulation. CONCLUSION: The development of electrical brainstem auditory potentials is not dependent on auditory stimulation.     

Role of auditory stimulation in maturation of the auditory pathway

Objective To compare the maturation of the auditory pathway, as shown by electrical brainstem auditory potentials (EABRs), in ears with and without prior auditory stimulation.

Material and Methods Electrophysiological data were collected prospectively from ears which had received cochlear implants. Implant-evoked (Imp)EABRs were recorded. Thirty children, implanted after January 2000, were selected according to a strict inclusion/exclusion protocol. All the children had received a 22-channel Nucleus cochlear implant (CI24 series). Intraoperatively, ImpEABRs were recorded using the Medelec Synergy® Evoked Response system in conjunction with Nucleus Neural Response Telemetry® software. The ImpEABR latencies of waves eII, eIII and eV and the morphology of wave eV were assessed.

Results ImpEABRs alter during the first 12 months of life. The latency becomes shorter during this period and the morphology of wave eV alters from a broad shape to a more distinct waveform. This appears to occur independently, even in the absence of auditory stimulation.

Conclusion The development of electrical brainstem auditory potentials is not dependent on auditory stimulation.     

Visual cognitive tests, central auditory function and auditory communication

A cognitive, text-based test battery, presented as text on a computer screen (TIPS), was used to assess properties of central cognitive processing relevant for visual and audiovisual speech comprehension. TIPS was compared and contrasted with another, purely auditory, battery, ACE, aimed at assessing afferent (A), central (C) and efferent (E) auditory communicative functions. The results show that there is no overlap with the 'A' component, but some overlap between TIPS parameters and the 'C' component, especially when the auditory-language tests are used in the C estimate. However, the TIPS parameters show high correlations with the 'E' component (i.e. measuring output and phonological parameters), suggesting that the efferent component may be composed of an interesting central feature. TIPS parameters do not fare as well in the predictions of the auditory ecological test performances, but the ACE parameters do, especially when organized according to a cognitive complexity parameter. In order to optimize the conceptual and practical benefit of the TIPS and ACE concepts, TIPS needs to be adapted auditorily and ACE tests need to be audiovisual. These developments will become important for ecological audiology.     

Central auditory function

Central auditory disorders in children and adults have become more widely recognized in patients seen by otolaryngologists and audiologists. This article briefly defines those clinical entities, discusses the historic background of testing, and describes current and future test approaches to assessment of central auditory disorders.     

Central auditory imperception

The development of clinically applicable techniques for the evaluation of hearing impairment caused by lesions of the central auditory pathways has increased clinical interest in the anatomy and physiology of these pathways. A conceptualization of present understanding of the anatomy and physiology of the central auditory pathways is presented. Clinical tests based on reduction of redundancy of the speech message, degradation of speech and binaural interactions are presented. Specifically performance-intensity functions, filtered speech tests, competing message tests and time-compressed speech tests are presented with the emphasis on our experience with time-compressed speech tests. With proper use of these tests not only can central auditory impairments be detected, but brain stem lesions can be distinguished from cortical lesions.