Potentiation of noise-induced hearing loss by amikacin in guinea pigs.

Noise and aminoglycosides initially attack cochlear outer hair cells (OHCs). Distortion product otoacoustic emissions (DPOAEs) are used for the early diagnosis of damage to OHCs. The effects of sub-damaging doses of amikacin, an aminoglycoside antibiotic agent, on noise-induced hearing loss (NIHL) were examined in guinea pigs. Animals were grouped by gender and exposed to broadband noise at 105 dB SPL for 12 h and/or injected i.m. with either amikacin (100 mg/kg/day) or saline for 10 days. Auditory brainstem response (ABR) thresholds, along with DPOAE amplitudes, were measured serially before and after noise exposure. DPOAE amplitudes decreased and ABR thresholds elevated immediately after noise exposure and then gradually recovered. At all frequencies, the emission amplitudes recovered completely to pre-exposure baseline values by 4 days after noise exposure. There was no effect of amikacin on either the ABR threshold or DPOAE amplitudes, in animals treated with amikacin only. However, amikacin significantly prolonged the effect of noise exposure on DPOAE amplitude but not on the noise-induced temporary threshold shift (TTS) of the ABR. In animals treated with a combination of noise and amikacin, significant changes in DPOAE amplitudes were still observed at 4 weeks after cessation of noise exposure. No gender difference in the responses to noise and/or amikacin could be demonstrated. The present findings indicate that even sub-damaging dosages of amikacin might impair recovery from NIHL in guinea pigs.     

Outer hair cells functionally and structurally deteriorate during reperfusion

Transient ischemia of the cochlea was induced in 65 albino guinea pigs by pressing the labyrinthine artery, and the effects of cochlear reperfusion on cochlear potentials (endocochlear potential, compound action potential and cochlear microphonics (CM)) and structural changes in hair cells were examined. Although 15 min ischemia did not elevate the post-ischemic CM pseudo-threshold as compared with the pre-ischemic value, ischemia of 30 min or longer significantly elevated the CM pseudo-threshold. CM amplitude tended to progressively decrease during the reperfusion period in the animals subjected to 45 or 60 min ischemia. After transient ischemia, outer hair cells (OHCs) were swollen and exhibited alterations of the nucleus. Severer structural deterioration of OHCs was induced by 4 h reperfusion than ischemia itself when the ischemic period was 45 or 60 min. Perilymphatic perfusion of dimethylthiourea, a hydroxyl radical scavenger, partially ameliorated the elevation of the CM pseudo-thresholds and the structural changes of OHCs. These results indicate that cochlear reperfusion induces functional and structural deterioration of OHC probably by hydroxyl radical generation.     

Poly(adenosine diphosphate-ribose) synthetase inhibitor 3-aminobenzamide alleviates cochlear dysfunction induced by transient ischemia

The present study was undertaken to determine the possible deleterious role played by poly(adenosine diphosphate-ribose) synthetase (PARS) in cochlear ischemia-reperfusion injury. Transient ischemia of the cochlea was induced in albino guinea pigs for 15, 30, or 60 minutes by pressing the labyrinthine artery at the porus acusticus internus. The animals were given intravenous 3-aminobenzamide (a PARS inhibitor) or physiological saline solution I minute before the onset of reperfusion. The compound action potential thresholds were measured before the onset of ischemia and 4 hours after the onset of reperfusion. A statistically significant reduction in the postischemic compound action potential threshold shift was observed in the animals treated with 3-aminobenzamide after 15 or 30 minutes of ischemia, whereas no statistical difference was found after 60 minutes of ischemia. These results suggest that excessive activation of PARS exerts deleterious effects on the cochlear injury induced by transient ischemia.     

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.     

Effects of industrial noise exposure on distortion product otoacoustic emissions (DPOAEs) and hair cell loss of the cochlea--long term experiments in awake guinea pigs

Distortion product otoacoustic emissions (DPOAEs), a sensitive detector of outer hair cell (OHC) function, cochlear microphonics (CM), and hair cell loss have been monitored in 12 awake guinea pigs before and after 2 h exposure to specific, played-back industrial noise (105 dB SPL maximal intensity). All animals had stable DPOAE levels before noise exposure. In the first hours after noise exposure DPOAE levels were reduced significantly. In about 70% a partial recovery of the DPOAEs was found within 4 months after noise exposure. In 16% of the investigated ears no recovery of DPOAEs was observed. However, in a few ears increased DPOAEs were observed after noise exposure. Exposure to industrial noise caused both morphological changes in the middle turns of the cochlea and electrophysiological changes in the middle frequency range. A close correlation existed between reduced DPOAE levels, loss in CM potentials, and area of damaged or lost OHCs, but not with the numbers of damaged or lost OHCs in the cochlea. It can be concluded that continuous industrial noise causes a damage to OHCs which differs form the damage caused by impulse noise.     

Effects of noise on the intensity of distortion product otoacoustic emissions

Distortion product otoacoustic emission (DPOAE) is a widely used differential diagnostic method for diagnosing inner ear disorders. It provides us information on the condition of the outer hearing cells (OHCs). Otoacoustic emission occurs only when the OHCs are functioning normally. Changes in thresholds of DPOAE curves can provide us important information on the activity of the OHCs. The inner ear shows nonlinear properties if the OHCs are functioning normally. If OHCs are injured and thus function improperly, the system stops showing nonlinear properties. If we have a system with periodic excitation and, with the addition of white noise, the signal-to-noise ratio on the output increases (at least for small noise intensities), we have witnessed what is called phenomenon stochastic resonance. Our goal was to elucidate how white noise influences the intensity of DPOAE. If there is emission, that specific ear surely exhibits nonlinear behavior, which in turn is the basic property needed for stochastic resonance.     

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.     

Neurotoxicity of BFM-95 on the medial olivocochlear bundle assessed by means of contralateral suppression of 2f1-f2 distortion product otoacoustic emissions.

OBJECTIVE: Berlin-Frankfurt-Munster 95 (BFM-95) is a common chemotherapeutic protocol against acute lymphoblastic leukemia (ALL). This prospective study investigates whether this protocol has an adverse effect on the medial olivocochlear bundle (MOCB) and/or outer hair cells' (OHCs) function. The distortion product otoacoustic emissions (DPOAEs) and their suppression by means of contralateral application of white noise were used for assessing the function of OHCs and the MOCB, respectively. STUDY DESIGN: Prospective study. SETTING: Oncology and otorhinolaryngology departments in a pediatric hospital. PATIENTS: Thirty-six children treated with ALL-BFM-95. INTERVENTIONS: Before chemotherapy, a baseline audiologic evaluation with tympanogram, standard and extended high frequency, pure-tone audiometry, and DPOAEs in the absence and presence of white noise was performed in all children. This population was divided in three groups. In a first group (n = 12), the evaluation was repeated after four sessions of vincristine administration; in the second group (n = 12), after 8 sessions; and in the third group (n = 12), several months after completion of the protocol. MAIN OUTCOME MEASURE: DPOAEs suppression by contralateral application of white noise. RESULTS: In the first and the third groups, we observed no changes in DPOAE amplitudes. Nevertheless, in the second group, the DPOAEs demonstrated significant decrease at 1416, 1685, 2002, and 2380 Hz. At baseline examination, all groups presented significant suppression at all frequencies. After eight vincristine sessions, instead of suppression, an increase of amplitudes was noted at 5 of 12 frequencies. Efferent-mediated DPOAE suppression reappeared in the third group at all frequencies (significant at 5 of 12 frequencies). CONCLUSION: ALL-BFM-95 seems to exert an early and reversible toxic effect on the MOCB, whereas its effects on OHCs are minimal and reversible. These minimal cochleotoxic and neurotoxic properties of ALL-BFM-95 might prove useful for research studies on the role of efferent innervation in hearing.     

次声波对豚鼠畸变产物耳声发射幅度的影响

目的观察强次声波暴露后豚鼠畸变产物耳声发射(DPOAE)的变化情况.方法将15只豚鼠置于频率8Hz、强度为135dB SPL的次声声场中连续暴露90分钟.分别于强次声波暴露前及暴露后即刻(2h内)、2天和5天做畸变产物耳声发射测试.结果强次声波暴露后豚鼠DPOAE的幅度值在各个频率段与暴露前相比均有明显的降低(p＜0.01),随着时间的推移,各个频率的幅度虽有一定的恢复,但仍明显低于暴露前水平(p＜0.01).结论强次声波可导致豚鼠耳蜗外毛细胞功能明显减退.     

Glucocorticoids and dehydroepiandrosterone sulfate ameliorate ischemia-induced injury of the cochlea

This study aimed to evaluate the effects of steroidal drugs on the functional recovery of the cochlea after transient ischemia. Albino guinea pigs were subjected to transient cochlear ischemia of 30 min duration, and the threshold shifts of the compound action potential (CAP) from the pre-ischemic values were evaluated 4 h after ischemia. Pre-ischemic administration of a glucocorticoid, prednisolone or methylprednisolone, significantly ameliorated the post-ischemic CAP threshold shifts as compared with control animals at a relatively wide range of doses. Post-ischemic administration of these glucocorticoids also exhibited protective effects. Pre-ischemic administration of dehydroepiandrosterone sulfate significantly decreased the post-ischemic CAP threshold shifts 4 h after ischemia. The present results indicate that glucocorticoids and dehydroepiandrosterone sulfate possess therapeutic effects against ischemic injury of the cochlea, such as idiopathic sudden sensorineural hearing loss.     

Contralateral suppression of distortion product otoacoustic emissions and the middle-ear muscle reflex in human ears

Distortion product otoacoustic emissions (DPOAEs) were measured in the absence and presence of contralateral noise at five levels--below, equal to, and above the middle-ear muscle (MEM) reflex threshold. The resultant changes in DPOAE level and phase were dependent on stimulus frequency and noise level. Both low-level noise, believed to elicit the medial olivocochlear (MOC) reflex, and high-level noise, thought to activate both MOC and MEM reflexes, significantly decreased the DPOAE level. However, the shift from sole MOC effect to mixed MOC and MEM effects was not as dramatic as we thought. While low-level noise resulted in a minimum DPOAE phase change, high-level noise caused a substantial phase lead for 1 and 2kHz. With increasing frequency, phase lag became more notable. The present study suggests the following: (1) DPOAE contralateral suppression by low-level sound most likely does not involve the effect of the MEM reflex and signal crossover; and (2) combined analysis of DPOAE level and phase changes warrants further investigations to overcome the difficulty in separating the effects of MOC efferents and MEM contraction. The results also imply that OAE measurement has the potential for being used to investigate the effect of the MEM reflex on sound transmission.     

Changes in distortion product otoacoustic emissions during prolonged noise exposure

The aim of this study was to evaluate the reduction in 2f₁−f₂ distortion product otoacoustic emission (DPOAE) amplitude resulting from prolonged noise exposures. A group of five chinchillas was exposed continuously to an octave-band noise centered at 4.0 kHz for a total of 42 days, 6 days at each of seven exposure levels. Exposure level increased in 8-dB steps from 48 to 96 dB SPL. DPOAE input-output (I/O) functions were measured at octave intervals over a range of primary tone f₂ frequencies between 1.2 and 9.6 kHz. Measurements were obtained (1) pre-exposure, (2) during days 3–6 of each 6-day exposure, and (3) 4 weeks after the final exposure. Continuous noise exposure caused a reduction in DPOAE amplitude that was greatest at f₂ frequencies within and above (3.4–6.8 kHz) the octave-band noise exposure. For these f₂ frequencies, DPOAE amplitudes decreased as exposure level increased up to approximately 72–80 dB SPL; higher exposure levels failed to cause any further reduction in DPOAE amplitude. The noise level at which DPOAE amplitude began to decrease was approximately 50 dB SPL. Above this critical level, DPOAE amplitude decreased 1.3 dB for every dB increase in noise level up to approximately 75 dB SPL.     

Effects of glucocorticoid receptor antagonist on CAPs threshold shift due to short-term sound exposure in guinea pigs

OBJECTIVE: The steroid drugs are used for the standard treatment of sudden sensorineural hearing loss. However, clinical results on the effect of glucocorticoids in acoustic trauma have not yet been understood well. The effects of glucocorticoid receptor (GR) antagonist, mifepristone, on the cochlea sensitivity loss due to short-term sound exposure were studied in the guinea pig. METHODS: Mifepristone (20 mg/kg) was injected subcutaneously immediately after the noise exposure to 4 kHz pure tone of 100 or 120 dB SPL for 10 min and also at 1 day and 3 days later. Seven days after the sound exposure, the compound action potentials (CAPs) of the cochlear nerve and the 2f(1)-f(2) distortion product oto-acoustic emissions (DPOAEs) were recorded. RESULTS: No significant CAP threshold losses were observed in either mifepristone or saline administration after the exposure at 100 dB SPL. After the exposure at 120 dB SPL, administration of mifepristone elevated the CAP threshold at 5-8 kHz significantly as compared with the saline administration. The DPOAE output shifts of both saline and mifepristone groups were similar to each other. CONCLUSION: Mifepristone may influence inner hair cells (IHCs) and afferent nerve fibers beneath the IHC without having influence on outer hair cells (OHCs). It is suggested that glucocorticoid plays an important role in the improvement of hearing impairment after loud sound exposure.     

Distortion-product otoacoustic emission (DPOAE) following pure tone and wide-band noise exposures

The aim of our investigations was to determine how the intensity of distortion-product otoacoustic emission (DPOAE) changes following different sound and noise exposures. We performed examinations on 20 healthy people with normal hearing. DPOAEs were recorded scanning the 0.5-6 kHz frequency interval before and after the exposures. We exposed the subjects to 0.5, 1, 2, 4 and 6 kHz pure tones and wide-band noise (intensity: 80 dB HL, duration: 3 minutes). We conclude that the amplitudes of DPOAEs changed immediately after exposures at most frequencies. DPOAE intensities decreased at some frequencies in the middle frequency range (1-2 kHz), and increased at low and particularly at high frequencies.     

豚鼠噪声暴露后畸变产物耳声发射及神经元特异性烯醇化酶表达的观察

为观察豚鼠暴露于强噪声后畸变产物耳声发射(DPOAE)及神经元特异性烯醇化酶(NSE)的变化,选用13只Preyer's反射正常的健康豚鼠,分为二组,8只噪声暴露组,5只为NSE表达对照组。噪声强度115dB(A),连续暴露4小时,DPOAE幅值于噪声暴露前后进行测试,结果DPOAE幅值噪声暴露前后差异明显(P<0.001),豚鼠内耳内、外毛细胞及螺旋神经细胞胞浆、隧道贯穿纤维NSE免疫组化反应均呈阳性表达,暴震前后无明显变化。结果提示豚鼠接受短时间强噪声刺激后,DPOAE幅值的下降为暂时阈移,而内耳神经元及其末梢未受损伤。     

Vulnerability of the gerbil cochlea to sound exposure during reversible ischemia.

Cochlear ischemia induces a sensorineural hearing loss, in part through a fast functional impairment of outer hair cellls. Assuming that the cochlea is rendered fragile during ischemia and reperfusion and that stimulation itself can jeopardize its functional recovery, we used a model of reversible selective cochlear ischemia in Mongolian gerbils to establish what type of sound exposure can be deleterious during and immediately after reversible ischemia. Several groups of gerbils were used, with different ischemia durations and levels of sound exposure. Control groups were only exposed to tones at 80 and 90 dB SPL during 30 min, while other groups underwent complete and fully reversible blockage of the labyrinthine artery, during 5.5 or 8 min, and were exposed to 60 or 80 dB SPL tones during 30 min. The amount of ischemia and reperfusion was measured by means of laser Doppler velocimetry, whereas outer hair cells' function was continuously monitored through distortion-product otoacoustic emissions (DPOAEs). The losses of DPOAE levels after 8 min transient ischemia and 60 dB SPL exposure were as large as those induced by 80 dB SPL exposures combined with 5.5 min ischemia, or 90 dB SPL exposures without ischemia, with a maximum loss around 25-30 dB, half an octave above the stimulus frequency. These results give evidence for an extremely high cochlear vulnerability to low-level sound exposure when associated with reversible ischemia. This vulnerability may have important clinical consequences in patients with cochlear circulatory disturbances.     

Assessment of outer hair cell function and blood antioxidant status of rabbits exposed to noise and metal welding fumes

OBJECTIVES: To investigate the interaction between welding fumes and noise in causation of hearing impairment. METHODS: Groups of rabbits (n=6) were exposed to noise, welding fumes or combination of both prior to Distortion Product Otoacoustic-Emissions (DPOAEs) analysis. The function of outer hair cells (OHCs) was examined by DPOAE assessment over a broad range of frequencies. Variations in DPOAE amplitude were compared between control (n=6) and exposed (n=18) groups. RESULTS: The DPOAEs levels measured at different frequencies (1379-6299 Hz) were found to decrease significantly (P<0.05) in rabbits exposed to 110 dB sound pressure level (SPL) broadband noise (8h/day, 12 days). In rabbits, exposed to carbon-steel welding fumes alone (157 mg/m(3)), the threshold shift was limited to the high frequencies (2759-6299 Hz), whereas, mixed exposure to noise and fumes resulted in reduction of DPOAEs at all the frequencies. Changes in DPOAEs were associated with increased susceptibility of erythrocytes to oxidation (P<0.05). Exposure to noise or fumes alone or simultaneously, suppressed total antioxidant ability of plasma as measured by ferric reducing ability of plasma (FRAP). Noise alone or in combination with fumes resulted in depletion of blood glutathione (GSH). Despite suppression of FRAP in the exposed groups, GSH was found to remain unchanged due to welding fumes suggesting that antioxidants other than GSH are affected by toxicants present in metal welding fumes. CONCLUSION: Exposure to very high levels of welding fumes can increase noise-related effects on OHC function by extending hearing threshold shift to wide band frequencies.     

The maximum permissible ambient noise and frequency-specific averaging time on the measurement of distortion product otoacoustic emissions

The effects of ambient noise and averaging time on distortion product otoacoustic emission (DPOAE) measurements were systematically examined in 20 normally hearing adults. For each frequency from 0.7 to 6 kHz, 2f1-f2 DPOAEs were measured at nine intensity levels of ambient noise for each of four different averaging times. The dependent variable of interest was the DPOAE:noise ratio (D:N)--the relationship between DPOAE amplitude and noise level at 2f1-f2. Findings indicated that, relative to the baseline condition (25 dBA), ambient noise levels of 40 dBA or greater affected the D:N considerably in the lower frequencies. However, noise levels of 55-65 dBA did not affect the D:N in the higher frequencies. Results also indicated that, to achieve detectable DPOAEs, longer averaging times were required as ambient noise increased and as frequency decreased. Based on the results, the maximum permissible ambient noise levels (MPANLs) were estimated in relation to averaging time.     

大鼠局灶性脑缺血再灌注后不同时相多胺含量的变化

目的 检测大鼠局灶性脑缺血再灌注不同时相脑皮质及皮质下多胺含量的变化，动态观察局灶性脑缺血再灌注后多胺含量变化的时相规律。方法 在Longa线栓法的基础上进行改良，复制大鼠2h局灶性脑缺血再灌注2、4、8、24h动物模型，用高效液相色谱法测定脑缺血区皮质和皮质下不同时相多胺的含量，分析其时相变化规律及意义。结果 实验组大鼠脑缺血区皮质和皮质下腐胺含量于再灌注4h后即开始逐渐升高（P〈0．05），高峰出现在再灌注24h后（P〈0．05）；再灌注8、24h实验组精脒、精胺含量较对照组明显下降（P〈0．05）。结论 局灶性脑缺血再灌注后腐胺含量增高，精脒、精胺含量减少，共同参与了脑缺血损伤。     

豚鼠畸变产物耳声发射潜伏期的对侧抑制效应现象

目的 通过观察对侧抑制效应中畸变产物耳发射（distortion productotoacousticemissions,DPOAE)各指标的改变,探讨耳蜗生理机制及传出神经的调节机能。方法 12只健康杂色豚鼠分A、B2组,在对侧耳无声刺激及给予70dB SPL宽带噪声条件下,分别使用不同的原始纯音强度组合测定在f2＝2、4、6kHz时测试耳DPOAE之幅值及潜伏期。次日,A组动物背侧径路开放右耳听泡,圆窗膜给予60mmol/L卡因酸1μL,作用3h后拭去。给药后6h测试右耳无声刺激和给予70dB SPL宽带噪声刺激下,左耳的DPOAE幅值、潜伏期等指标。结果 ①用药前,A组对侧耳给声时以等强度原始音诱发的测试耳DPOAE各频率幅值与给声前基本无变化,而潜伏期显著延长;②用药前,B组对侧耳给声以差强度原始音（L2＝L1－10dB)诱发的测试耳DPOAE在2、4kHz的幅值与给声前相比有显著减小,潜伏期也显著延长;③A组用药后,对侧耳给声对测试耳DPOAE幅值和潜伏期均无显著影响。结论 潜伏期亦是对侧抑制研究中的敏感指标。对侧抑制效应在调制耳蜗转导机制中发挥负反馈作用。