低供氧对清醒豚鼠耳蜗功能的影响

通过圆窗电极保持豚鼠在清醒状态下面罩供应５％氧及９５％氮混合气体３０分钟，记录耳蜗神经动作电位（ＡＰ）、总和电位（ＳＰ）以及微音器电位（ＣＭ）的改变，以提供低氧状态下清醒豚鼠的全耳蜗电生理反应的模型。实验发现：供５％氧后，１６ｋＨｚ声刺激下，ＡＰ振幅急剧下降；８及２ｋＨｚ声刺激下ＳＰ振幅明显增大；ＣＭ有所下降，但程度较轻；并可导致０．２５～３２ｋＨｚ全频程的１５～３０ｄＢ的ＡＰ暂时性阈移；正常供氧后，以上改变逐渐复原。１０只实验豚鼠对５％氧的耳蜗电位反应形式基本一致，但程度有不同。实验发现，低供氧所致ＡＰ变化，在高强度声刺激和阈值强度声刺激时的结果有分离现象，认为上述耳蜗电生理变化是由于低供氧导致了耳蜗能量（ＡＴＰ）减少，蜗内电位降低，并引起了神经传输（传入、传出或交感神经）功能的紊乱。     

低供氧对清醒豚鼠耳蜗功能的影响

通过圆窗电极保持豚鼠在清醒状态下面罩供应５％氧及９５％氮混合气体３０例钟，记录耳蜗神经动作电位，总和电位以及微音器电位的改变，以提供低氧状态下清醒豚鼠的全耳蜗电生理反应的模型。实验发现：供５％氧后，１６ｋＨｚ声刺激下，ＡＰ振幅急剧下降；８及２ｋＨｚ声刺激下ＳＰ振幅明显增大；ＣＭ有所下降；但程度较轻；并可导致０．２５－３２ｋＨｚ全频程的１５－３０ｄＢ的ＡＰ暂时性阈移；正常供氧后，以上改变逐渐复原。１     

畸变产物耳声发射幅值与超高频纯音听阈的关系

目的 探讨畸变产物耳声发射（ｄｉｓｔｏｒｔｉｏｎ ｐｒｏｄｕｃｌｓ ｏｔｏａｃｏｕｓｔｉｃ ｅｍｍｉｓｓｉｏｎ，ＤＰＯＡＥ）与超高频纯音听阈用于早期耳蜗性听力损害的听力监测的可能性。方法 ＤＰＯＡＥ以配对初始音诱发，两音强度均为７０ｄＢ ＳＰＬ，频率比为１：１．２，频率范围０．５￣８ｋＨｚ。测定常规频率（１２５Ｈｚ￣８ｋＨｚ）及超高频率（９￣２０ｋＨｚ）的纯音听阈。比较正常听阈组与不正常听阈值的Ｄ     

硝普钠耳毒作用的内耳靶组织

作为细胞内及细胞间的一种信息传递分子，一氧化氮（ｎｉｔｒｉｃｏｘｉｄｅ，Ｎ０）成为近年来医学界的一个研究热点。而硝普钠（ｓｏｄｉｕｍｎｉｔｒｏｐｒｕｓｓｉｄｅ，ＳＮＰ）作为ＮＯ的供体亦被广泛应用于动物及临床实验。晚近报道，ＳＮＰ可抑制听神经复合动作电位（ｃｏｍｐｏｕｄａｃｔｉｏｎｐｏｔｅｎｔｉａｌ，ＣＡＰ），其耳毒作用机制尚不清楚。本实验旨在结合各种电生理学方法及病理学检查，探讨ＳＮＰ耳毒作用的靶组织，并间接观察ＮＯ对耳蜗各结构功能的影响。结果发现：圆窗膜上或鼓阶内给予不同浓度ＳＮＰ１μｌ后，豚鼠耳蜗血流量增加，而蜗内电位（ｅｎｄｏｃｏｃｈｌｅａｒｐｏｔｅｎｔｉａｌ，ＥＰ）迅速下降，ＣＡＰ反应阈明显提高，耳蜗微音电位（ｃｏｃｈｌｅａｒｍｉｃｒｏｐｈｏｎｉｃ，ＣＭ）及耳声发射畸变产物（Ｆ２－Ｆ１）之耳蜗微音电位（ｃｏｃｈｌｅａｒｍｉｃｒｏ－ｐｈｏｎｉｃｑｕａｄｔａｔｉｃｄｉｓｔｏｒｔｉｏｎｐｒｏｄｕｃｔ，ｃｍＱＤＴ）下降；基底膜振动速度反应（ｖｅｌｏｓｉｔｙｒｅｓｐｏｎｓｅｏｆｂａｓｉｌａｒｍｅｍｂｒａｎｅｖｉｂｒａｔｉｏｎ，ＶＲＢＭＶ）下降；内放射纤维水肿。实验揭示，ＳＮＰ急性耳毒作用具有浓度及时间相关性，     

聚DL-天冬氨酸对庆大霉素耳毒性拮抗作用的实验研究

目的　研究聚ＤＬ天冬氨酸（ｐｏｌｙ ＤＬａｓｐａｒｔｉｃ ａｃｉｄ,ＰＡＡ） 对Ｆ３４４ 大鼠庆大霉素（ｇｅｎｔａｍｉｃｉｎ,ＧＭ） 耳毒性的拮抗作用。方法　选用健康Ｆ３４４ 大鼠５０ 只,随机分４ 组：Ⅰ为ＧＭ、Ⅱ为ＰＡＡ＋ ＧＭ、Ⅲ为ＰＡＡ、Ⅳ为生理盐水对照组;通过观测４ 组大鼠不同时期、不同频率听性脑干反应（ａｕｄｉｔｏｒｙ ｂｒａｉｎｓｔｅｍ ｒｅｓｐｏｎｓ,ＡＢＲ）阈值的改变;计数耳蜗毛细胞死亡率,以观察ＰＡＡ对Ｆ３４４ 大鼠ＧＭ 耳蜗毒性的拮抗作用;用双向扩散血清培养基检测法观察ＰＡＡ 对ＧＭ 抗菌活性的影响。结果　Ⅰ组短纯音１０ ｋＨｚ、８ ｋＨｚ ＡＢＲ阈值与其他３ 组差异有显著性（ Ｐ＜ ０．０１） ,给药１８ ｄ 耳蜗毛细胞死亡率与其他３ 组间差异也有显著性（ Ｐ＜０ ．０１）。结论　ＰＡＡ对庆大霉素的耳毒性具有拮抗作用,且不减低其抗菌活性。     

正常清醒豚鼠的畸变产物耳声发射特性

目的 研究正常清醒豚鼠的畸变产物耳声发射（ＤＰＯＡＥ）的特性。方法 采用ＣＥＬＥＳＴＡ ５０３型耳声发射分析仪对２６只正常清醒豚鼠（３５耳）进行ＤＰ图及ＤＰ输入／输出曲线（ＤＰ－Ｉ／Ｏ）的测试，随机选择１１只正常清醒豚鼠（２０耳）进行ＤＰＯＡＥ的重复测试，用ＳＰＳＳ１０．０对数据进行统计分析。结果 在ＤＰ图中，当初始音强度Ｌ１／Ｌ２为 ７０／６５ ｄＢ ＳＰＬ时，正常清醒豚鼠的 ＤＰＯＡＥ幅值随测试频率ｆ０从０．７５－８ｋＨｚ的增加而逐渐升高（２７．９０±１．９６－5０．６５±０．７１）。在 ＤＰ－Ｉ／Ｏ中，当ｆ０分别为４、６、８ ｋＨｚ时，正常清醒豚鼠的ＤＰＯＡＥ幅值随Ｌ１／Ｌ２从７０／６５以５ｄＢ－挡降至１５／１０ ｄＢ ＳＰＬ而呈线性下降（Ｐ＜０．０１），在Ｌ１／Ｌ２为５５／５０或６０／５５ ｄＢ ＳＰＬ处出现饱和或低谷，同一Ｉ／Ｏ曲线上Ｌ１／Ｌ２分别从７０／６５及５５／５０ ｄＢ ＳＰＬ递减至阈值的Ｉ／Ｏ斜率（分别记为ＫＴ及ＫＬ）均接近于１，且ＫＬ大于ＫＴ（Ｐ＜０．０１）。重复测试的ＤＰＯＡＥ幅值差异小（＜ １ｄＢ ＳＰＬ）且无统计学意义（Ｐ＞０．０５）。结论 正常清醒豚鼠ＤＰＯＡＥ测试充分表现了其捡出率高、反应幅值大     

沙土鼠在听力学研究中的应用

听力学是二战后由Ｄａｖｉｓ将其发展成专门研究听觉生理、病理和听觉障碍诊断、处理的一门独立学科。近年来,人们发现沙土鼠耳蜗结构与豚鼠十分类似,但高频听力比豚鼠敏锐,尤其在高频听力具有优势,其高频听力可达到４０～５０ｋＨｚ;沙土鼠的耳声发射更易引出;沙土鼠对电刺激诱发更敏感,如电刺激诱发的耳声发射（ｅｌｅｃｔｒｉｃａｌｌｙ　ｅｖｏｋｅｄ　ｏｔｏａｃｏｕｓｔｉｃ　ｅ－ｍｉｓｓｉｏｎ,ＥＥＯＡＥ）、电刺激诱发的听性脑干反应（ＥＡＢＲ）等都更易引出,更稳定。另外,沙土鼠饲养成本较豚鼠更低廉,且抵抗力较豚鼠…     

豚鼠耳蜗微血管SP受体阳性结构的观察

目的探讨ＳＰ（ｓｕｂｓｔａｎｃｅＰ）调节耳蜗血流的作用机理。方法本研究采用免疫组织化学ＡＢＣ技术结合葡萄糖氧化酶－ＤＡＢ－镍染色法,观察豚鼠耳蜗微血管ＳＰ受体的分布状态。结果豚鼠耳蜗基底膜各圈均可见ＳＰ受体阳性的微血管,阳性结构主要位于血管内膜,呈密度增高的线状分布。结论作用于耳蜗微血管内膜ＳＰ受体的ＳＰ,主要来源于血液及内皮细胞自身。     

缺氧缺血性脑病新生儿瞬态诱发耳声发射测试

目的了解应用瞬态诱发性耳声发射（ｔｒａｎｓｉｅｎｔｅｖｏｋｅｄｏｔｏａｃｏｕｓｔｉｃｅｍｉｓｉｏｎｓ,ＴＥＯＡＥ）对正常新生儿高危新生儿行听力筛查的可行性。方法采用ＳＦ－Ⅰ型耳声发射接受器与ＣｏｍｐａｃｔＡｕｄｉｔｏｒｙＴＩＰ－３００电反应测听仪联合记录,对２０名正常新生儿及３６名缺氧缺血性脑病（ｈｙｐｏｘｉａ－ｉｓｃｈｅｍｉｃｅｎｃｅｐｈａｌｏｐａｔｈｙ,ＨＩＥ）新生儿进行ＴＥＯＡＥ和ＡＢＲ测试。结果ＨＩＥ患儿ＴＥＯＡＥ多表现为阈值升高或波缺失,ＴＥＡＯＥ能否出现与ＡＢＲ之Ｖ波阈值密切相关,重度ＨＩＥ的ＴＥＯＡＥ出波率较轻度者明显减低。结论ＴＥＯＡＥ可早期发现缺氧等高危因素所致听力损伤,因此有可能成为早期监测新生儿及高危儿听力的一种方法。     

豚鼠畸变产物微音器电位与畸变产物耳声的发射的相关？…

为探讨畸变产物微间电位（ＤＰＣＭ）是否畸变产物耳声发射（ＤＰＯＡＥ）引发，将豚鼠的ＤＰＯＡＥ和ＤＰＣＭ同时叠加，发现在较高强度的声刺激下（ｆ０＝１００６Ｈｚ，ｆ０＝２０１１Ｈｚ，ｆ０＝４０３３Ｈｚ），ＤＰＣＭ叠加结果与ＤＰＯＡＥ各峰有一一对应的关系，ＣＭ的２ｆ１－ｆ２峰相对值（与ｆ１峰比值）比ＤＰＯＡＥ的２ｆ－ｆ２要小得多。较低声强刺激时（ｆ０＝１００６Ｈｚ〈５０ｄＢ，ｆ０＝２０１１Ｈｚ〈６０ｄＢ     

镇静及麻醉剂对耳蜗传出神经系统功能的影响

目的 观察镇静、麻醉状态下维持体温时对侧噪声对圆窗记录的耳蜗神经电生理活动（electrophysiological cochleoneural activity)的 抑制效应，探讨镇静及麻醉剂对耳蜗传出神经系统功能的影响。方法 采用圆窗慢性电极记录耳蜗神经电生理活动并获得其平均功率谱（average spectrum of electrophysiological cochleoneural activity,ASECA)；分别肌注2％xylazine(10mg/kg)用于镇静及2％xylazine(10mg/kg)和ketamine(50mg/kg)的混合剂用于麻醉。通过对侧噪声的抑制试验评价耳蜗传出神经系统功能。结果 实验结果表明，镇静状态下无论体温维持与否，对侧噪声抑制效应减弱，而麻醉状态下，对侧抑制效应几乎消失。说明耳蜗传出神经功能分别受到部分和完全抑制。结论 镇静剂，尤其是麻醉剂对听觉系统的传出神经功能均产生影响，建议在进行耳蜗传出神经功能的研究中应使动物或实验对象处于清醒状态下进行，如确实需要干预，则只能选择镇静方式并注意采用小剂量，对结果的解释应慎重。     

Frequency-dependence of early auditory evoked responses in the guinea pig

Summary Neural auditory responses in the guinea pig, monitored by surface electrodes (brain stem potentials and frequency-following responses) and by electrodes at the round window, were analyzed for evidence of frequency dependence in the range from 500 Hz to 15 kHz. The characteristics of the brain stem potentials and frequency-following responses with stimuli near threshold intensity for frequencies below 2 kHz indicate that this activity derives from the excitation of apical regions of the basilar membrane. The same interpretation applies to the potentials recorded at the round window. Comparison of the responses seen with surface electrodes and those appearing at the round window reveals that the broad potential P_I of the brain stem response to low-frequency stimuli corresponds to the compound action potential, while the frequency-following responses correspond to phase-locked responses in the acoustic nerve.     

Ensemble spontaneous activity in the guinea-pig cochlear nerve

Spectral analysis of electrical noise recorded from the round window (RW) of the cochlea is referred to as the ensemble spontaneous activity (ESA) of the cochlear nerve. The ESA is considered to represent the summed spontaneous activity of single fibers of the auditory nerve and changes in the spectral characteristics of the ESA have been observed in humans with tinnitus. Experiments were undertaken to determine the relationship of the ESA to auditory neurotransmission. The ESA consisted of energy centered at approximately 900 Hz, similar to the spectral peak of single auditory neuron discharges. The amplitude of the ESA was correlated with good auditory sensitivity in the 12-30 kHz region of the cochlea. Constant pure tones of 12-22 kHz suppressed the ESA reducing its amplitude in a frequency and intensity dependent manner implying that the ESA recorded at the RW is generated or dominated by neurons in the basal region of the cochlea. The ESA was significantly suppressed by round window perfusion of the P2X receptor agonist adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) (10 mM) the glutamate receptor antagonist 6-7-dinitroquinoxaline-2,3-dione (DNQX) (1 mM), and the sodium channel antagonist tetrodotoxin (TTX) (20 microM). Following intravenous furosemide injection (40 mg/kg) reduction and recovery of the ESA correlated with similar changes in the endocochlear potential (EP). Following DNQX and ATPgammaS an additional spectral peak at 200 Hz was often observed. This peak has been postulated to be a correlate of tinnitus in humans but had not previously been observed in a guinea-pig model of tinnitus. These data confirm the spectral characteristics of the ESA in guinea-pigs and show it is dependent on the sensitivity of the auditory nerve and intact auditory neurotransmission. In addition these experiments support the view that the ESA represents summed spontaneous neural activity in the cochlea and provide a platform for studies of the influence of ototoxic compounds on the spontaneous neural outflow of the cochlea as a model of tinnitus.     

Similar half-octave TTS protection of the cochlea by xylazine/ketamine or sympathectomy

Cochlear efferents, sympathetic control and stress conditions have been shown to influence sound-induced hearing loss. These factors are also known to be modified by sedation/anesthesia. We tested here the effect of sedation/anesthesia on temporary threshold shift (TTS) compared to that in the same awake animals. The effect of sympathectomy was also tested. We employed awake guinea pigs with a chronically implanted electrode on the round window of each of the cochleae. Each ear was tested for its sensitivity to TTS induced by a 1 min or a 10 min exposure to an 8 kHz pure tone at 96 dB sound pressure level. After an intramuscular injection of xylazine or ketamine together with xylazine, TTS at half-octave frequencies was reduced compared to that in awake animals. The second half-octave frequencies were less affected. This specific pattern of protection was also observed here after surgical ablation of a superior cervical ganglion. The data lead to the speculation that protection from TTS under sedation/anesthesia might be due to diminished sympathetic influence. Xylazine is a pre-synaptic alpha2-adrenoreceptor agonist which blocks noradrenaline release from the sympathetic system. Ketamine is a N-methyl-D-aspartic acid receptor antagonist which could reduce glutamate excitotoxicity as well as reduce sympathetic activity.     

The origin of the 900 Hz spectral peak in spontaneous and sound-evoked round-window electrical activity

We have monitored the spectrum of the (spontaneous) neural noise at the round window (RW) and on the surface of the antero-ventral cochlear nucleus (CN) and the dorsal CN (DCN) of anaesthetised guinea pigs. We have also obtained the average gross extracellular waveform evoked by 20 kHz tone-bursts (0.25 ms and 25 ms) at each of these recording sites, and calculated the spectrum of the average waveforms (SAW). With these tone-bursts, only a small population of neurones in the extreme basal turn of the cochlea near the RW electrode responds, presumably with only a single action potential for each 0.25 ms tone-burst. The RW waveforms recorded between 20 dB and 60 dB SPL were very similar, and are therefore presumably a simple estimate of the shape of the contribution of the firing of a single neurone to the gross RW signal (the unitary potential or UP). In normal animals, the SNN and the SAW were remarkably similar, with peaks at 900 Hz and at 2400 Hz, suggesting that they are not due to neural synchronisation (as suggested previously by others), but are due to an oscillatory waveform produced by each single fibre action potential. Abolition of all spike activity by RW tetrodotoxin left a waveform with only a summating potential and a dendritic potential, and no 900 Hz peak in the SAW or SNN, indicating that the spectral peak is due to neural spiking only. Abolition of the CN contribution to the RW waveforms by CN application of lignocaine or sectioning of the cochlear nerve at the internal meatus (by focal aspiration of the DCN and underlying cochlear nerve) showed that the 900 Hz peak was not simply due to the addition of a delayed and inverted CN contribution: mathematical modelling shows that this would produce a broad spectral peak at about 1200 Hz. Moreover, the 900 Hz spectral peak remains after complete abolition of the CN contribution, although reduced in amplitude. This residual 900 Hz peak can be traced to an oscillation in the gross waveform due to the presence of two peaks (P(1)* and N(2)*) which follow the intact N(1) peak. The P(1)* and N(2)* peaks were present at the RW, but not at the cochlear nerve as it exits the internal meatus, suggesting that they were not due to double-spiking of some of the neurones, but were probably due to a sub-threshold electrical resonance in the peripheral dendrites. We have successfully modelled the production of the SNN and the compound action potential and SAW in response to 0.25 ms and 25 ms tone-bursts at 20 kHz by including only a damped 900 Hz resonance in the UP, without refractory effects, preferred intervals or synchronisation in the timing of neural spike generation. Such resonances in other neurones are known to be due to the activation kinetics of the voltage-controlled sodium (Na(+)) channels of these neurones. The presence of such sub-threshold oscillations probably indicates that the peripheral dendrites are devoid of stabilising potassium (K(+)) channels. We also discuss the role of this membrane resonance in generating burst-firing of the cochlear nerve (as with salicylate) and the role of such burst-firing in generating tinnitus.     

Effects of endotoxin on the cochlear electrophysiology and Na(+)-K(+)-ATPase activity

Hemophilus influenzae (type B) endotoxin 10 micrograms was put in the niche of the round window in guinea pigs. The CAP thresholds and N1 latencies were measured before and 12, 24 and 72 hours after experiments. The 10 kHz and 8 kHz CAP thresholds after experiments were significantly higher (P less than 0.01), the N1 latencies were prolonged (P less than 0.05). There were minute changes in 4kHz CAP thresholds and N1 latencies (P greater than 0.05). In all time groups, the Na(+)-K(+)-ATPase activity was outstandingly weakened. It suggested that: (1) endotoxin put in the niche of the round window is responsible for the cochlear function disturbances in high frequencies, and (2) the decrease of the Na(+)-K(+)-ATPase activity is an important factor for the electrophysiological disturbances in the inner ear.     

Factors affecting hearing results after stapes surgery.

Factors affecting auditory improvement after stapes surgery were investigated retrospectively on a study group of 106 otosclerotic ears (86 subjects). While the closure of the air-bone (A-B) gap after surgery was good at 2 kHz and 4 kHz, it was poor at 8 kHz and at frequencies lower than 1 kHz. Under 1 kHz, the lower the frequency, the worse the A-B gap after surgery. Stapedotomy and partial stapedectomy showed better post-operative hearing gain at 4 kHz than total stapedectomy. Total stapedectomy scored significantly better at 250 Hz and 500 Hz than stapedotomy. There was a close relationship between the pre-operative and post-operative A-B gap at frequencies under 1 kHz. The smaller the pre-operative A-B gap, the better the closure of the post-operative A-B gap at these frequencies. It was speculated that otosclerotic ears with a larger pre-operative airbone gap might have another lesion in the middle ear other than the oval window.     

Cochlear potentials and their modulation by low-frequency sound in early endolymphatic hydrops

Seventeen guinea pigs were unilaterally operated to produce endolymphatic hydrops. After 2 wk (9 animals) or 4 wk (8 animals), extracochlear electrophysiological responses to tone bursts of several frequencies were recorded in both the operated and non-operated ears. In addition, modulation by low-frequency (29 Hz sinusoidal bias) sound of the responses to 8 kHz tonebursts was measured. After the electrophysiological measurements, the animals were killed and examined histologically. Four weeks after the operation, cochlear microphonics in response to a 500 Hz tone burst and to the 29 Hz bias were significantly smaller in the operated ears. The summating potential showed a tendency to be larger in the operated ears. The compound action potential input-output curves for 2 kHz probes showed a small threshold shift accompanied by steep slopes, reminiscent of recruitment. Modulation of summating potentials by the low-frequency bias was smaller on the operated side. In most cochleae an endolymphatic hydrops was observed. Three cochleae showed a collapse of Reissner's membrane.     

Rapidly fluctuating thresholds at the onset of experimentally-induced hydrops in the guinea pig

Pigmented guinea pigs were chronically implanted bilaterally with a platinum electrode on each round window. After recovery the endolymphatic sac was destroyed and the duct blocked on one side only; the other side was employed as a control. The round window response thresholds on both sides were recorded several times per week over a three month period. There were three main results. A sensitivity loss of up to 20 dB was observed for frequencies between 250 Hz and 6.4 kHz within two weeks post-op. At the end of three months the threshold elevation for these frequencies was as much as 50 dB. On the other hand the thresholds for frequencies between 8 and 16 kHz remained within 10 dB of their pre-operative value for at least two months. The thresholds fluctuated with a shift of as much as 25 dB within 24 h. The threshold elevation was associated with a decrease in the latency, at threshold, of the round window AP response which at frequencies between 250 Hz and 6.4 kHz was as short as that for 8 kHz. This observation suggested that it was the base, only, of the cochlea which responded. The present study has indicated that experimentally induced endolymphatic hydrops in the guinea pig mimics well the progressive and fluctuating hearing loss characteristic of Ménière's disease.     

Effects of 250 and 500 Hz tone exposure on the inner ear of guinea pigs as determined by electrophysiological techniques

The electrophysiological study of cochlear microphonics (CM), whole nerve action potential (AP) and endocochlear potential (EP) were examined. (1) With the extension of the exposure time of 500 Hz tone, a decrease of CM maximum output voltage in test frequency from 2 to 6 kHz was observed. (2) N1 potential of AP decreased very significantly by 500 Hz tone exposure. (3) A very pronounced decrease of the absolute value of the negative potential of the EP in 500 Hz exposure was seen.