豚鼠外淋巴瘘对畸变产物耳声发射的影响

为观察豚鼠外淋巴瘘造模后畸变产物耳声发射的变化，选用１１只豚鼠右耳为实验耳，手术建立蜗窗外淋巴瘘。在实验前，打开听泡，蜗窗膜造瘘，缝合伤口及外淋巴瘘造后１８天，均以２ｆ１－ｆ２ｚＤＰＯＡＥ的幅值记录其变化。测试完毕后豚鼠耳蜗行火棉胶包埋切片，观察形态学改变。结果发现在形成蜗窗膜外淋巴瘘前后ＤＰＯＡＥ幅值变化差异有显著性（Ｐ〈０．０１），１８天后蜗窗膜愈合者ＤＰＯＡＥ幅值明显提高，接近实验前，而未愈     

畸变产物耳声发射临床应用价值的探讨

研究了７３例（１３９耳）纯音听阈正常耳及各种感音神经性聋耳的ＤＰＯＡＥ，发现ＤＰＯＡＥ对耳蜗功能异常的改变早于纯音测听，并可精确地反映耳蜗毛细胞在相关频率上的功能状态；ＤＰＯＡＥ幅值及引出率随纯音听阈的提高而下降，当纯音听阈＞５０ｄＢ（ＨＬ）时，ＤＰＯＡＥ幅值明显降低或缺失；蜗后病变耳ＤＰＯＡＥ正常，当蜗后病变累及耳蜗时，ＤＰＯＡＥ幅值可异常，其异常程度与纯音听阈不平行。认为ＤＰＯＡＥ有广泛临床应用价值。     

士的宁阻断橄榄耳蜗束对豚鼠畸变产物耳声发射的影响

为探讨豚鼠听觉中枢对畸变产物耳声发射（ＤＰＯＡＥ）的影响，利用士的宁阻断听觉系统的传出神经，系统观察了阻断前后ＤＰＯＡＥ的变化。结果发现在本实验条件下，所有豚鼠均可引出ＤＰＯＡＥ，在同等刺激强度和Ｌ１＝Ｌ２的情况下，低频ｆ０＝１００６Ｈｚ的ＤＰＯＡＥ强度大，而较高频ｆ０＝２０１１和ｆ０＝４０３３的ＤＯＰＡＥ强度较小。士的宁阻断橄榄耳蜗束对ＤＰＯＡＥ无影响，提示在正常神经张力下中枢不参与、不影响ＤＯ     

卡因酸耳蜗毒性的电生理学研究

目的：观察谷氨酸类受体激动剂卡因酸（ＫＡ）对豚鼠耳蜗的毒性作用。方法：健康杂色豚鼠８只，每只动物经圆膜给予６０ｍＭ ＫＡ１μｌ，于用药前及用药后１２ｈ分别检测听神经复合动作电位（ＣＡＰ），耳蜗微音电位（ＣＭ）和畸变产物耳声发射（ＤＰＯＡＥ）之２ｆ２－ｆ２。结果：用药后ＣＡＰ明显下降或消失（Ｐ〈０．００１），而ＣＭ和ＤＰＯＡＥ无明显变化。结论：ＫＡ对初级听觉传入神经末梢具有选择性毒性作用。     

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     

畸变产物耳声发射对侧抑制效应的临床应用价值

目的：为观察畸变产物耳声发射（ＤＰＯＡＥ）对侧抑制效应的临床应用价值。方法：研究以白噪声为对侧声刺激,对１７例正常人（３４耳）,１３例蜗性聋（１３耳）,９例蜗后聋（９耳）进行了ＤＰＯＡＥ及其对偶抑制效应测试。结果：蜗性聋耳的ＤＰＯＡＥ幅值较正常耳显著下降（Ｐ〈０．０１）,对偶抑制效应减弱,但与正常人差异无统计学意义（Ｐ〉０．０５）,蜗后聋耳ＤＰＯＡＥ幅值高于正常耳（Ｐ〉０．０５）,对侧抑制效应显著     

外淋巴钙离子对畸为产物耳声发射的影响

目的 研究外毛细胞运动产生畸产产物耳声发射（ＤＰＯＡＥ）的机理。方法 观察９只豚鼠（１１耳）采用无钙和有钙的人工外淋巴灌流外淋巴腔后ＤＰＯＡＥ的变化。结果 用无钙人工外淋巴灌流后ＤＰＯＡＥ的均值从４１．３ｄＢＳＰＬ降至１３．７ｄＢＳＰＬ，再用正常钙浓度的外淋巴灌流后又可回升到３６．７ｄＢＳＰＬ结论 ＤＰＯＡＥ的产生需外淋巴强正常浓度的钼离耿必要条件。提示外毛细胞在产生ＤＰＯＡＥ中并非以毛细胞的电运     

外淋巴钙离子对畸变产物耳声发射的影响

目的研究外毛细胞运动产生畸变产物耳声发射（ＤＰＯＡＥ）的机理。方法观察９只豚鼠（１１耳）采用无钙和有钙的人工外淋巴灌流外淋巴腔后ＤＰＯＡＥ的变化。结果用无钙人工外淋巴灌流后ＤＰＯＡＥ的均值从４１．３ｄＢＳＰＬ降至１３．７ｄＢＳＰＬ，再用正常钙浓度的外淋巴灌流后又可回升到３６．７ｄＢＳＰＬ。结论ＤＰＯＡＥ的产生需外淋巴中正常浓度的钙离子为必要条件。提示外毛细胞在产生ＤＰＯＡＥ中并非以毛细胞的电运动性机制起作用，而是与一般肌纤维相似的收缩机理起作用，需要钙离子的中介。     

正常新生儿畸变产物耳声发射

目的研究新生儿畸变产物耳声发射（ＤＰＯＡＥ）听力筛选的最佳时机,了解正常新生儿ＤＰＯＡＥ的基本特征;方法应用Ｃｅｌｅｓｔａ５０３型耳声发射分析仪对２０名正常新生儿出生后１～５天逐日进行ＤＰＯＡＥ测试。结果随新生儿天龄的增加,ＤＰＯＡＥ的检出率及反应幅值逐渐提高。ｆ０为０．５ｋＨｚ时,ＤＰＯＡＥ的检出率较低,且反应不稳定。ｆ０≥０．７５ｋＨｚ时,ＤＰＯＡＥ的检出率迅速接近或达到１００％,大部分测试频率在出生１～２天的反应幅值显著低于后几天,至出生后第３天,ＤＰＯＡＥ的检出率及反应幅值均趋于稳定;结论新生儿ＤＰＯＡＥ听力筛选的适宜天龄应在其出生后３天或３天以上。０．５ｋＨｚ不宜作为新生儿ＤＰＯＡＥ的听力筛选频率。ＴＥＯＡＥ和ＤＰＯＡＥ相应频谱的反应幅值有显著相关性。两种耳声发射在新生儿听力筛选中各有优缺点     

切断听神经对豚鼠DPOAE的影响

利用手术切断听的方法分离中枢与外周耳蜗的神经联系，观察分离前后ＤＯＡＥ的变化。在本实验条件下，所有豚鼠均可引出ＤＰＯＡＥ，在同等刺激强度和Ｌ１＝Ｌ２的情况下，低频ｆｏ＝１００６Ｈｚ的ＤＰＯＡＥ强度大，而较主频ｆ０＝２０１１和ｆ０－４０３３Ｈｚ的ＤＰＯＡ强度较小，切断听神经对ＤＰＯＡＥ无影响，无噪声状态下中枢不参与、不影响ＤＰＯＡＥ的产生和形成，打开豚鼠骨大泡，可引起ＤＰＯＡＥ明显下降，经分析发现主     

Protective effects of glucocorticoids on ischemia-reperfusion injury of outer hair cells

OBJECTIVE: This animal study aimed to investigate effects of glucocorticoids on the functional recovery of outer hair cells (OHCs) after transient ischemia. METHODS: Distortion-product otoacoustic emission (DPOAE) was examined before, during, and after transient cochlear ischemia of 30 minutes using albino guinea pigs. RESULTS: DPOAE decreased to noise level during ischemia. On recirculation, DPOAE initially recovered with time until 20 minutes after the onset of reperfusion, but thereafter, the DPOAE level gradually decreased toward the noise level in the control animals. Prednisolone and methylprednisolone significantly improved the DPOAE level 60 minutes after the onset of reperfusion. CONCLUSIONS: The present findings suggest that glucocorticoids possess protective effects against ischemia-reperfusion injury of OHCs.     

Cisplatin ototoxicity in developing gerbils.

This experimental study was undertaken to investigate the dose-related effect of cisplatin exposure in young gerbils (2 weeks of age) and explore the relationship between different methods used to monitor auditory function after exposure to cisplatin. Four groups of animals, including a control group, were used. The treatment groups, D1 (n = 6), D2 (n = 7) and D3 (n = 6), received one, two, and three doses of cisplatin (5 mg/kg/dose), respectively, at weekly intervals. Treated animals were first exposed to cisplatin at 2 weeks of age. Distortion product otoacoustic emissions (DPOAE) and auditory brainstem responses (ABR) were measured in treated and control animals at 6 weeks of age. The effects of dose and frequency on the DPOAE amplitude, as well as the relationship between the DPOAE and the ABR thresholds were analyzed. Animals in the D1 and D3 groups demonstrated significant elevation of DPOAE and ABR thresholds. Interestingly, animals in the D2 group demonstrated a bimodal distribution of DPOAE and ABR responses, with four animals severely affected and three not showing an effect. A tendency for a bimodal distribution of DPOAE and ABR responses was also observed in the D1 group, at frequencies below 8 kHz.     

Protective effect of thymoquinone against cisplatin-induced ototoxicity

The aim of this study was to investigate the potential protective effect of thymoquinone against cisplatin-induced ototoxicity. This study is a prospective, controlled experimental animal study. Experiments were performed on 30 healthy female Sprague-Dawley rats. Thirty animals were divided into three groups of 10 animals each. Group 1 received an intraperitoneal (i.p.) injection of cisplatin 15 mg/kg. Group 2 received i.p. thymoquinone 40 mg/kg/day for 2 days prior to cisplatin injection and third day i.p. cisplatin 15 mg/kg was administered concomitantly. Group 2 continued to receive i.p. thymoquinone until fifth day. Group 3 received i.p. thymoquinone 40 mg/kg/day for 5 days. Pretreatment distortion product otoacoustic emissions (DPOAE) and auditory brain stem responses (ABR) testing from both ears were obtained from the animals in all groups. After the baseline measurements, drugs were injected intraperitonally. After an observation period of 3 days, DPOAE measurements and ABR testing were obtained again and compared with the pretreatment values. There was no statistically significant difference between pre and post-treatment DPOAE responses and ABR thresholds group 2 and 3. However, group 1 demonstrated significant deterioration of the ABR thresholds and DPOAE responses. Our results suggest that DPOAE responses and ABR thresholds were preserved in the cisplatin plus TQ-treated group when compared with the group receiving cisplatin alone. According to these results, cisplatin-induced ototoxicity may be prevented by thymoquinone use in rats.     

Is there a close relationship between changes in amplitudes of distortion product otoacoustic emissions and hair cell damage after exposure to realistic industrial noise in guinea pigs?

In long-term experiments in awake guinea pigs (n=12), distortion product otoacoustic emissions (DPOAEs) at various frequencies were measured repeatedly over 6–8 months. About 9 weeks after the first measurement, the animals were exposed to industrial noise (car industry, maximal intensity about 110 dB SPL) for 2 h. The amplitudes of DPOAE were measured prior to noise exposure and 10 min, 70 min, 1 day and 2 days after the noise exposure and then once every week. Three to four months after noise exposure, the animals were killed, and the cochleae were prepared for scanning electron microscopy. The row of inner hair cells (IHCs) was complete in all animals, while the rows of outer hair cells (OHCs) showed a considerable hair cell loss in some of the animals without a correlation to the change in amplitudes of DPOAE. However, a closer relationship between the decline of amplitudes of DPOAE and the number of missing and changed OHCs (fused stereocilia bundles, missing tip links) could be established. The number of lost OHC does not reflect the decline in DPOAE in all cases. This discrepancy must be considered when the degree of hearing loss needs to be established from changed DPOAE.     

Role of mannitol in reducing postischemic changes in distortion-product otoacoustic emissions (DPOAEs): a rabbit model

OBJECTIVES: The aim of this study was to observe the effects of mannitol, administered topically at the round window (RW), on cochlear blood flow (CBF) and distortion-product otoacoustic emission (DPOAE) after repeated episodes of cochlear ischemia. METHODS: Ten young rabbits were used for this study. Reversible ischemic episodes within the cochlea were induced by directly compressing the internal auditory artery (IAA). CBF was measured using a laser-Doppler (LD) probe positioned at the RW niche. DPOAEs were measured at 4, 8, and 12 kHz geometric mean frequency (GMF) using 60 dB sound pressure level (SPL) primary tone stimuli. In five test ears, mannitol was administered topically at the RW for 30 minutes before the IAA compressions. In five control ears, the IAA compressions were undertaken without application of RW medication. Each ear underwent three 5 minute IAA compressions with a 60 minute rest period between compressions. RESULTS: In the control animals, it was observed that a progressive reduction in DPOAE level followed each successive IAA compression at all three test frequencies. The reduction in DPOAE amplitudes was consistently greater at the higher test frequencies. In the test rabbits, the RW administration of mannitol resulted in significantly less reduction in DPOAE level measures after repeated IAA compressions. For example, 30 minutes after reperfusion at 12 kHz GMF, DPOAE levels in the control ears were reduced by 1.5, 6.0, and 16 dB, compared with 1.5, 4.0, and 6.0 dB in the mannitol test ears. CONCLUSIONS: Mannitol appears to exert a protective effect on cochlear function after periods of ischemia. The RW appears to be an efficacious route for topical administration of mannitol into the inner ear.     

内耳疾病基因治疗方法的研究

目的:探讨一种高效、安全和简便的内耳疾病基因转移和导入方法。方法:将30只健康豚鼠随机分为A、B、C 3组,每组10只。用Ad—GFP报告基因分别由圆窗、耳蜗底回和脑脊液三种途径导入30只豚鼠内耳,在术前和术后测定听性脑干反应(ABR)阈值和畸变产物耳声发射(DPOAE)振幅改变。再行耳蜗铺片,观察AdGFP在内耳组织中的转染表达和耳蜗毛细胞的形态结构。结果:三种途径导入Ad—GFP在耳蜗螺旋神经节、血管纹和Corti器上均有转染和表达。在术后3 d的表达产物最高,7 d后减弱,10 d后更弱。圆窗和耳蜗底回钻孔导入手术可引起蜗内出血,凝血块淤积在耳蜗顶回的中阶,造成顶回毛细胞损害。而脑脊液给药途径无此现象。ABR阈值在各组动物手术前后无明显改变,而圆窗和耳蜗底回给药途径造成DPOAE幅度明显下降,脑脊液给药组无DPOAE改变。结论:应用腺病毒载体进行基因转移通过圆窗和耳蜗底回钻孔途径可引起蜗内出血,影响DPOAE幅度,而应用脑脊液给药途径则相对安全和方便。     

Cisplatin-induced ototoxicity and pharmacokinetics: preliminary findings in a dog model

The early effects of a clinical dose of cisplatin (100 mg/m2) on distortion-product otoacoustic emissions (DPOAE) thresholds and the relationship between DPOAE threshold shifts and changes in plasma concentrations of filterable and total platinum (Pt) following infusion of cisplatin in a dog model were investigated. The DPOAE thresholds (based on input-output function) were measured 2 days before a single high dose of cisplatin administration, and compared with measurements recorded 2 and 4 days after infusion. The results revealed DPOAE thresholds to be elevated by 4 days after the administration of cisplatin. However, this elevation could not be correlated with plasma concentrations of filterable and total Pt, which showed little variation over the 48-hour postinfusion period between animals. The present study demonstrated that DPOAE thresholds have the potential to be used as an indicator of cisplatin-induced ototoxicity, and cisplatin-induced ototoxicity could not be explained by plasma Pt kinetics in individual animals.     

Exploring efferent-mediated DPOAE adaptation in three different guinea pig strains

The aims of this study were to explore the correlation between DPOAE adaptation magnitude in three different guinea pig strains to examine if the genetic component affects the DPOAE adaptation magnitude. It was also to investigate the correlation between strains with certain characteristics i.e. reduced susceptibility to noise, and early onset of age-dependent hearing loss and the DPOAE adaptation magnitude. The animals were anaesthetized and the 2f1-f2 DPOAE (f1=8k Hz, and f2/f1=1.2) adaptation was established with a minimum of 144 combinations of f1; f2 where f1 was held fixed and f2 was varied in 1 dB or 0.4 dB steps. The DPOAE adaptation magnitude was defined as the difference between maximum positive level and the maximum negative level. ABRs were conducted at different age-groups (at 4, 6.3, and 12.5k Hz) to evaluate the progress of hearing thresholds by age. There was a significant difference between strains regarding the hearing loss at one year of age. There was no significant difference in DPOAE adaptation magnitude between strains included in this study and from this we conclude that the DPOAE adaptation magnitude is not a predictor for the susceptibility to noise trauma, or early onset of age-dependent hearing loss, using the methods described in this paper.     

Frequency-specific cochlear damage in guinea pig after exposure to different types of realistic industrial noise

For the causal evaluation of occupational hearing damage it is important to identify definitely the noise source. Here we tested, whether recordings of distortion product otoacoustic emissions (DPOAEs) in awake guinea pigs can distinguish the effects of different industrial noises. Six groups of 12 animals each were investigated before and over four months after a single 2 h exposure to specific, played-back industrial noise as well as before and for 2 months after impulse noise exposure. We compared broadband noise (buzz saw, bottle washing machine), low frequency noise (drawing press), and mid-frequency noise (bottle filling machine). All animals had stable DPOAE levels before noise exposure. Frequency specific decreases in DPOAEs were found after exposure to the different noises. Broadband noise diminished mostly all frequencies tested, whereas low- or mid-frequency noise had a greater effect on DPOAE evoked by middle and higher frequencies, respectively. DPOAE evoked by middle and higher frequencies were obliterated after impulse noise. Morphological analysis of the cochleae confirmed these alterations. OHC loss was found in the middle turns of the cochleae corresponding to the diminution of DPOAE. We conclude that different kinds of industrial noise tend to produce typical changes in DPOAE levels.