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.     

The effect of various durations of noise exposure on auditory brainstem response, distortion product otoacoustic emissions and transient evoked otoacoustic emissions in rats

This study was designed to investigate the effect of various durations of noise exposure in animals on physiological responses from the cochlea which are also used clinically in humans: auditory brainstem response (ABR), transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs). Rats were exposed to 113 dB SPL broad-band noise (12 h on/12 h off) for durations of 3, 6, 9, 12, 15 and 21 days, and tested 24 h after cessation of the noise and again after a period of 6 weeks. ABR threshold to click stimuli and to a 2-kHz tone burst (TB), TEOAE energy content and DPOAE amplitude in the exposed rats were compared to those in a group of control rats not exposed to noise. ABR thresholds (click and TB) were significantly elevated in all exposure duration groups compared to control rats. DPOAE amplitudes and TEOAE energy content were significantly reduced. The mean ABR thresholds following 21 days exposure were significantly greater (click = 100 dB pe SPL; TB = 115 dB pe SPL) than those following 3 days exposure (click = 86 dB pe SPL; TB = 91 dB pe SPL). Linear regression analysis between recorded responses and duration of noise exposure (days) showed a significant increase in ABR thresholds of approximately 0.8-- 1.4 dB/day. TEOAE and DPOAE responses showed no such dependence on noise duration and were already maximally reduced after only 3 days of exposure. This can be explained by the possibility that short noise exposures may cause damage to the early, more active stages of cochlear transduction (as shown by TEOAEs and DPOAEs). As the noise exposure continues, further damage may be induced at additional, later stages of the cochlear transduction cascade (as shown by ABR). Thus, ABR seems more sensitive to noise duration than OAE measures.     

Effects of alcohol and noise on temporary threshold shift in Guinea pigs

The purpose of this study was to investigate the effects of concomitant exposure to noise and alcohol on the auditory thresholds. Twenty-four guinea pigs were equally divided into three groups: the acute intoxication group, the chronic intoxication group and the control group. Animals in the acute group received single intraperitoneal injections of ethanol (2 g/kg). In the chronic group, alcohol was administered via drinking water (10%, v/v) over a 60-day period. All animals were exposed to a white noise at the intensity of 105 dB A for 30 min. Auditory brainstem response (ABR) thresholds and distortion product otoacoustic emission (DPOAE) levels were measured before, immediately after noise exposure and also 1, 2, and 7 days following exposure. The results showed: first, acute alcohol injection caused a significant, temporary elevation of ABR threshold (4.8 dB in average), while chronic alcohol treatment did not change auditory threshold significantly. Second, noise exposure induced a mean threshold shift of 15.4- 19.7 dB. ABR threshold returned to normal 2 days after exposure. Both acute and chronic alcohol treatment did not alter the magnitude and time course of recovery of the temporary threshold shift (TTS). Third, the mean DPOAE amplitudes decreased at most frequencies following acute injection of alcohol. However, the differences did not reach statistical significance. Fourth, the mean DPOAE levels dropped 3.4-9.6 dB in all groups after noise exposure and returned to normal 1 day to 2 days after noise. There were no significant differences in the amount of DPOAE suppression after noise between the three groups. In summary, we have found that acute and chronic treatment of alcohol in combination with noise did not significantly exacerbate TTS or decrease DPOAE amplitudes relative to noise exposure alone.     

Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic emissions in laboratory animals

OBJECTIVE: The role of transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) as early indicators of cisplatin-induced ototoxicity in three different rodent species--the guinea pig. the albino rat, and the fat sand rat (Psammomys obesus)--was investigated. In addition, an attempt was made to determine which of the three rodent species is most susceptible to cisplatin-induced ototoxicity as measured by auditory brainstem responses (ABR), BACKGROUND: There have been numerous clinical and experimental reports on cisplatin-induced ototoxicity, but to the authors' best knowledge, there has been no comparative report on the short-term effects of cisplatin on OAE measured with commercially available equipment between different rodent species. METHODS: Cisplatin was systemically administered as a single high dose (12 mg/kg intraperitoneally) to all three species, and the ototoxic effects were measured before and 3 days after the injection of cisplatin in the same animals, using ABR, TEOAE, and DPOAE. RESULTS: The ABR thresholds were significantly elevated in the guinea pigs and the albino rats but not in the sand rats. Significant depression of TEOAE energy and DPOAE amplitude occurred only in the guinea pigs. The depression of the DPOAE was greater than that of the TEOAE. The guinea pigs showed the greatest degree of ototoxicity (depression of ABR and OAE). CONCLUSIONS: Among the three rodent species, the guinea pig has the potential to be used as a sensitive animal model in studies of cisplatin ototoxicity. The study also showed that the recordings of TEOAE and DPOAE, in addition to ABR, are sensitive techniques for the assessment of cisplatin-induced ototoxicity.     

纯中药制剂复聪汤对庆大霉素致聋豚鼠耳蜗毛细胞修复再生的实验研究

目的观察纯中药制剂对庆大霉素致聋动物和耳蜗毛细胞的修复再生作用。方法选用73只健康青年豚鼠,行听力学检查后,53只动物连续肌肉注射庆大霉素(80mg.kg-1.d-1)24～30天致聋(GM组),其间死亡8只,剩余45只随机分成中药治疗组(25只)和致聋后对照组(20只),中药治疗组给予纯中药制剂"复聪汤Ⅰ号"口服液和"复聪汤Ⅱ号"滴耳液治疗,致聋后对照组同法给予生理盐水。另外20只豚鼠作为正常对照组,每天肌肉注射等量生理盐水。在治疗30、60和90天后对GM组两组动物分别行ABR、DPOAE检测,同时,每一时间点处死6只动物,左侧耳蜗行扫描电镜观察,右侧耳蜗铺片行光镜观察和毛细胞计数。结果实验前所有豚鼠的听功能正常;连续注射庆大霉素30天后,GM组豚鼠ABR反应阈值上升到50～80dB SPL,DPOAE幅值降低,光镜和电镜下表现为耳蜗毛细胞纤毛断碎、倒伏、融合和消失,多处毛细胞表皮板肿胀、突起和疱疹样变性,或毛细胞被完全挤出网状板,基底回和第三回耳蜗毛细胞严重消失;中药治疗30天后,80%的耳聋豚鼠的ABR反应阈恢复到30～50dB SPL,DPOAE幅值明显提高;耳蜗铺片和电镜观察显示耳蜗毛细胞数目有一定恢复,组织结构有修复现象,扫描电镜可见再生毛细胞仅出现少量纤毛,而致聋后对照组未发现此种现象;治疗60天后,耳蜗毛细胞数目明显增多,Corti器的毛细胞区有大量的增殖细胞出现,扫描电镜可见成小束的新生纤毛出现在毛细胞缺失部位,同时支持细胞大量增殖;治疗90天后,再生的静纤毛束已基本形成,尤其是耳蜗基底部位的毛细胞明显增多,听功能基本正常。结论纯中药制剂复聪汤对庆大霉素致聋豚鼠耳蜗毛细胞有一定的修复和再生作用。     

模拟失重及飞船内稳态噪声对大鼠听功能的影响

目的 探讨模拟失重及飞船舱内中等强度稳态噪声对大鼠听功能影响的时效关系。 方法 96只雄性SD大鼠随机分为失重组、噪声组、失重+噪声组和对照组,各24只鼠,每组大鼠再按暴露时间随机分为1周、4周组,各12只鼠,最后在暴露结束后即刻(P0)测听并处死一半大鼠作为暴露即刻组,另一半脱离暴露环境7 d后(P7)测听并处死作为恢复组,各6只鼠。失重模拟采用尾部悬吊即Morey Holton法模拟失重,噪声模拟采用白噪声信号发生系统模拟飞船舱内中等强度稳态噪声［8 h/d 的(72±2)dB SPL稳态噪声+16 h/d的(50±2)dB SPL稳态噪声］。分别在暴露前(B0)、P0、P7检测ABR阈值和畸变产物耳声发射(DPOAE)。 结果 失重组、噪声组、失重+噪声组和对照组的ABR阈值在暴露1周P0时分别为(10.83±5.25)、(8.13±4.62)、(13.54±8.53)、(7.08±2.52)dB SPL;在暴露1周P7时分别为(6.67±2.46)、(5.83±1.95)、(8.75±4.33)、(7.92±3.34)dB SPL;在暴露4周P0时分别为(18.13±7.19)、(16.04±5.71)、(19.58±8.33)、(6.04±2.54)dB SPL;在暴露4周P7时分别为(7.92±3.96)、(7.92±3.34)、(14.17±7.93)、(6.25±2.26)dB SPL。失重组和失重+噪声组大鼠暴露1周后ABR阈值较暴露前升高,且随时间延长进一步加重,噪声组ABR阈值在暴露1周时与暴露前差异无统计学意义(P=0.054),在暴露4周时升高;失重+噪声暴露4周组ABR阈值在P7时与P0时差异无统计学意义,未见恢复,其余暴露组在P7时ABR阈值完全恢复。暴露前后各实验组DPOAE引出率无统计学差异。 结论 失重及稳态噪声对听功能的损伤有明显的时间累积效应,二者具有协同作用且失重占据主导。4周模拟失重或飞船舱内中等强度稳态噪声单独暴露导致的大鼠ABR阈移是可逆的,但4周的复合暴露可能已造成不可逆性听损伤,且主要损伤内毛细胞的功能。     

Effects of exposure of the ear to GSM microwaves: in vivo and in vitro experimental studies

The effects of mobile phone (GSM) microwaves on the ears of guinea pigs were investigated in two in vivo experiments and one in vitro experiment. In the first experiment, three groups of eight guinea pigs had their left ear exposed for 1 h/day, 5 days/week, for 2 months, to GSM microwaves (900 MHz. GSM modulated) at specific absorption rates (SARs) of 1, 2 and 4 W/kg respectively, and a fourth group was sham-exposed. Distortion-product otoacoustic emissions (DPOAEs) were measured for each ear before exposure, at the end of the 2-month exposure period, and 2 months later. In the second experiment, the same protocol was applied to eight sham-exposed and 16 exposed guinea pigs at 4W/kg, but the auditory brainstem response (ABR) thresholds were monitored. Repeated-measures ANOVA showed no difference in DPOAE amplitudes or in ABR thresholds between the exposed and non-exposed ears and between the sham-exposed and exposed groups In the course of the second experiment, acute effects were also investigated by measuring once, in all animals, ABR thresholds just before and just after the 1-h exposure: no statistically significant difference was observed. In vitro, the two organs of Corti (OCs) of newborn rats (n=15) were isolated and placed in culture. For each animal, one OC was exposed for 24-48 h to 1 W/kg GSM microwaves, and the other was sham-exposed. After 2-3 days of culture, all OCs were observed under light microscopy. They all appeared normal to naive observers at this stage of development. These results provided no evidence that microwave radiation, at the levels produced by mobile phones, caused damage to the inner ear or the auditory pathways in our experimental animals.     

A Method for Establishing an Animal Model of Like-Auditary Neuropathy

Objective: To establish an animal model of like-auditory neuropathy in neonatal rat. Methods The ani-mals were injected with phenylhydrazine hydrochloride or saline at 7-day of age. ABR and DPOAE were performed to assess the auditory function. The cochlea basilar membrane stretched preparation and cochlear frozen sections were prepared for immunohistochemical staining to examine the morphological change of hair cells and spiral ganglion cells (SGNs). Results At 7-day age the ABR waveI, III, V, latencies andI-III,I-V IWIs in the experimental group were significantly prolonged compared with those in the control group. The ABR thresholds were also elevated in the experimental group. We found there is no significant differ-ence in DPOAE in phenylhydrazine hydrochloride exposure group compare to control group. The cochlear hair cells showed no signs of loss in both group, but the total number of neurofilaments positive cells in SGNs were significantly reduced in the phenylhydrazine treated animals. Conclusion Our study suggests that phenylhydrazine hydrochloride can change the auditory function and induce peripheral nerve pathology by targeted mainly the SGNs in neonatal rat.     

Hyaluronan applied to lesioned round window membrane is free from cochlear ototoxicity

Hyaluronan (HYA) in 1% solution was instilled into the round window (RW) niche of rats (n = 6) prior to perforating the round window membrane (RWM). Cochlear functioning and structure were then monitored by recording auditory brainstem responses (ABRs) at 2-31.5 kHz and by scanning electron microscopy. Perforation of the RWM alone (n = 6) resulted in immediate loss of ABR thresholds between 6 and 31.5 kHz in 2 of 6 animals. Similar results were obtained after instilling HYA into the RW niche and subsequent RWM perforation (n = 6). After 2 months, ABR thresholds were recorded at all frequencies in the HYA-treated animals, whereas in 2 of the controls no ABR thresholds could be elicited at 20 and 31.5 kHz. However, in both treatment groups the mean ABR thresholds and mean latencies for wave II at the ABR threshold returned to the pre-surgical (normal) range after 2 months. With respect to the cochlear morphology the results in both treatment groups were also alike including minor structural changes in hair cell stereociliae but no loss of hair cells. It is concluded that HYA, when instilled into the middle ear with the inner ear opened, is free from cochlear otoxicity.     

Otoacoustic emission, evoked potential, and behavioral auditory thresholds in the rhesus monkey (Macaca mulatta).

Distortion product otoacoustic emission (DPOAE), auditory brainstem evoked response (ABR), and behavioral thresholds were recorded in a group of 15 adult rhesus monkeys with normal auditory function. DPOAE thresholds were recorded with stimulus parameters selected to maximize signal-to-noise ratio. Additional averaging at the lowest frequencies ensured comparable noise levels across frequencies. DPOAE thresholds decreased with increasing frequency (f(2)=0.5-16 kHz) and at 16 kHz were close to 0 dB SPL. ABR thresholds were best from 1 through 16 kHz (32-38 dB peSPL); higher at 0.5 (45 dB peSPL), 24 (39 dB peSPL), and 30 kHz (49 dB peSPL). At all levels including threshold, the early ABR waves (II and I) were more prominent at the high frequencies while the later waves (IV and V) were more prominent at the low frequencies. The behavioral thresholds recorded were similar to those reported by other researchers although elevated by about 10 dB presumably because of the complexity of the threshold task. DPOAE and ABR thresholds can be reliably and efficiently recorded in the rhesus monkey and provide information concerning site of processing in the auditory pathway not directly available from behavioral data.     

强脉冲噪声暴露后大鼠听皮层蛋白质差异表达的研究

目的 运用蛋白质组学技术检测强脉冲噪声暴露后不同时间点大鼠听皮层蛋白质表达谱的差异.方法 健康成年SD大鼠分为三组:正常对照组、急性脉冲噪声暴露组及噪声暴露后恢复组.脉冲噪声平均压力峰值(声压级)为156 dB,脉宽为0.25 ms,暴露50次.听性脑干反应(ABR)评价大鼠听功能;运用二维凝胶电泳+质谱分析法对各组大鼠听皮层蛋白质表达谱进行检测,比较其差异,并对表达变化较大的蛋白进行质谱鉴定.结果 与对照组相比,急性暴露组及恢复组在ABR各频率(2、4、8、16、32 kHz)阈值均明显提高(P值均＜0.05);噪声暴露即刻,ABR各频率听阈均有40 ～60 dB的上升;暴露后第7天,各频率ABR阈值有所恢复,第14天时趋于稳定.噪声暴露前后听皮层组织中的差异蛋白有64个,选取变化倍数大的50个点进行酶切质谱鉴定.其中有14个点不可信,剩余36个点所代表的27种蛋白被鉴定出来.所鉴定的差异蛋白主要包括:细胞骨架相关蛋白,线粒体及能量代谢相关蛋白,与突触重塑、神经递质释放及神经元兴奋性相关的蛋白等.结论 强脉冲噪声暴露可引起大鼠听皮层中多种蛋白质表达的变化,这些差异蛋白可能参与强噪声听力损伤的修复过程,以及听觉中枢的可塑性变化及功能重组.     

听性稳态诱发反应在听力异常婴儿的诊断意义

目的听性稳态诱发反应（auditory steady—statere sponse，ASSR）新技术与视觉强化测听（vision reinforcement audiometry，VRA）阈值的相关性分析研究，探讨听神经病症侯群及其鉴别诊断。方法10例（20耳）对照组，年龄6～12个月，测得ASSR和VRA的正常阈值。16例（26耳）异常听力组患儿（年龄在3～6个月），根据其所患疾病分为3个亚组：Ⅰ组为早孕感染组5例（8耳），Ⅱ组为窒息缺氧组5例（10耳），Ⅲ组为高胆红素血症组6例（8耳），检测畸变产物耳声发射（DPOAE）、听性脑干反应（ABR）潜伏期、肌反射值与ASSR和VRA及其相关性结果对照。结果Ⅰ组中2例次（2耳次）为单纯疱疹病毒感染。5例次（8耳次）DPOAE消失，4例次（6耳次）ABR波Ⅰ潜伏期延长、Ⅰ—Ⅴ波间潜伏期缩短，3例次（6耳次）500Hz和1000Hz的镫骨肌反射正常，2例次（2耳次）镫骨肌反射阈偏高，初步推测单纯耳蜗性病变，排除听神经病可能，测得ASSR平均估计阈值与VRA平均阈值具有很好的相关性（r=0．95～0．98）。Ⅱ组中4例次（8耳次）畸变产物耳声发射消失，其中1例次（2耳次）ABR波Ⅰ、波Ⅲ、波Ⅴ消失和肌反射消失，3例次（5耳次）ABR波Ⅰ消失和波Ⅲ及波Ⅴ潜伏期延长，以及肌反射消失。2例次（3耳次）Ⅰ-Ⅲ波间潜伏期延长，肌反射也消失。推测可能为听神经病症侯群（耳蜗至脑干下听觉传导通路受损）伴有耳蜗功能障碍，测得ASSR平均估计阈值与VRA平均阈值具有较好的相关性（r=0．72～0．84）。Ⅲ组中6例次（8耳次）DPOAE存在，4例次（5耳次）ABR波Ⅰ、Ⅲ、Ⅴ和肌反射消失，2例次（3耳次）Ⅰ—Ⅴ波间潜伏期延长，镫骨肌反射阈正常偏高，初步分析推测为听神经病症侯群病损在脑干以上，测得ASSR平均估计阈值与VRA平均阈值具有很弱的相关性（r=0．43～0．64），ASSR阈值和VRA阈值不一致，进一步说明这组的病损应该在脑干或皮层。3个亚组的每个频率（0．25、0．5、1、2,4kHz）平均ASSR和VRA阈值差值比较，差异都具有统计学意义（F检验，P〈0．05、P〈0．01、P〈0．01、P〈0．05、P〈0．05）。结论通过ASSR阈值和VRA阈值相关性技术研究或许可提供诊断及鉴别诊断在各种频率听力障碍婴儿的听神经病症侯群（病变高位）、听神经病症侯群伴有耳蜗功能障碍（病变低位）以及单纯耳蜗性病（非听神经病）。     

Effects of cisplatin on the auditory function of ovariectomized rats with estrogen deficiency

Conclusion: The ovariectomy in rats does not change their auditory function. However, combining ovariectomy with Cisplatin treatment increases the risk of damaging the auditory function relative to the ototoxic effect caused by Cisplatin alone or ovariectomy alone.

Objectives: The auditory benefit from estrogen depends on a number of factors that make findings among studies controversial. The present study was to examine the impact of Cisplatin, a chemotherapy drug, on the auditory function of ovariectomized rats.

Methods: Thirty-two female rats were assigned to three groups (OVX?+?C, OVX???C, Sham?+?C). The rats in the OVX?+?C and OVX???C groups received bilateral ovariectomy, and those in the Sham?+?C group received a sham surgery with intact ovaries. After 6 weeks the rats in the OVX?+?C and Sham?+?C groups were then treated with Cisplatin for 4 days, but not those in the OVX???C group (control). The auditory function was measured with DPOAE SNRs and ABR thresholds before the surgery and after the Cisplatin treatment.

Results: The OVX?+?C group had significantly decreased the DPOAE SNRs and increased the ABR thresholds relative to the Sham?+?C group at stimulus frequencies between 2–8?kHz, and the Sham?+?C group also had worse auditory function than the OVX???C group.     

Effects of repeated "benign" noise exposures in young CBA mice: shedding light on age-related hearing loss

Temporary hearing threshold shift (TTS) resulting from a "benign" noise exposure can cause irreversible auditory nerve afferent terminal damage and retraction. While hearing thresholds and acute tissue injury recover within 1-2 weeks after a noise overexposure, it is not clear if multiple TTS noise exposures would result in cumulative damage even though sufficient TTS recovery time is provided. Here, we tested whether repeated TTS noise exposures affected permanent hearing thresholds and examined how that related to inner ear histopathology. Despite a peak 35-40 dB TTS 24 hours after each noise exposure, a double dose (2 weeks apart) of 100 dB noise (8-16 kHz) exposures to young (4-week-old) CBA mice resulted in no permanent threshold shifts (PTS) and abnormal distortion product otoacoustic emissions (DPOAE). However, although auditory brainstem response (ABR) thresholds recovered fully in once- and twice-exposed animals, the growth function of ABR wave 1( p-p ) amplitude (synchronized spiral ganglion cell activity) was significantly reduced to a similar extent, suggesting that damage resulting from a second dose of the exposure was not proportional to that observed after the initial exposure. Estimate of surviving inner hair cell afferent terminals using immunostaining of presynaptic ribbons revealed ribbon loss of ～ 40 % at the ～ 23 kHz region after the first round of noise exposure, but no additional loss of ribbons after the second exposure. In contrast, a third dose of the same noise exposure resulted in not only TTS, but also PTS even in regions where DPOAEs were not affected. The pattern of PTS seen was not entirely tonotopically related to the noise band used. Instead, it resembled more to that of age-related hearing loss, i.e., high frequency hearing impairment towards the base of the cochlea. Interestingly, after a 3rd dose of the noise exposure, additional loss of ribbons (another ≈ 25 %) was observed, suggesting a cumulative detrimental effect from individual "benign" noise exposures, which should result in a significant deficit in central temporal processing.     

Effects of acute infrasound exposure on vestibular and auditory functions and the ultrastructural changes of inner ear in the guinea pig]

OBJECTIVE: To define the effects of acute infrasound exposure on vestibular and auditory functions and the ultrastructural changes of inner ear in guinea pigs. METHODS: The animals involved in the study were exposed to 8 Hz infrasound at 135dB SPL for 90 minutes in a reverberant chamber. The sinusoidal pendular test (SPT), auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) were respectively detected pre-exposure and at 0(within 2 hrs), 2 and 5 day after exposure. The ultrastructures of the inner ear were observed by scanning electron microscopy. RESULTS: The slow-phase velocity and the frequency of the vestibular nystagmus elicited by sinusoidal pendular test (SPT) declined slightly following infrasound exposure, but the changes were not significant (P > 0.05). No differences in the ABR thresholds, the latencies and the interval peak latencies of I, III, V waves were found between the normal and the experimental groups, and among experimental groups. The amplitudes of DPOAE at any frequency declined remarkably in all experimental groups. The ultrastructures of the inner ear were damaged to different extent. CONCLUSION: Infrasound could transiently depress the excitability of the vestibular end-organs, decrease the function of OHC in the organ of Corti and cause damage to the inner ear of guinea pigs.     

急性次声波暴露后豚鼠位听功能及内耳超微结构的变化

目的观察次声波对豚鼠位听功能和内耳超微结构的影响。方法将豚鼠置于频率8Hz、声压级135dBSPL的次声声场中连续暴露90min。应用正弦摆动试验(sinusoidalpendulartest,SPT)、听性脑干反应（auditorybrainstemresponse,ABR）和畸变产物耳声发射(distortionproductionotoacousticemission,DPOAE)评价次声波暴露前后豚鼠前庭功能和听功能的变化,扫描电镜观察豚鼠内耳各结构表面超微形态的变化。结果次声波暴露后不同时间正弦摆动诱发的豚鼠前庭性眼震的最大慢相速度(slow-phasevelocity,SPV)和频率较次声暴露前轻微降低,但无显著性意义(P>0.05)。次声波暴露后各组动物ABR阈值较正常时略有升高,亦无统计学差异(P>0.05),各组动物ABR各波潜伏期和波间期与次声暴露前比较差异均无显著性(P>0.05);DPOAE的幅度值在各个频率段均有明显的降低(P<0.01)。扫描电镜下见各实验组动物内耳半规管壶腹嵴两囊斑及Corti器感觉毛细胞纤毛缺失、散乱、倒伏及融合,表皮板等结构均有不同程度的损伤。结论次声波对豚鼠前庭末梢感受器兴奋性可能有一过性的轻微抑制作用,但SPT无有意义改变。次声波可引起豚鼠内耳毛细胞超微结构的损伤,可导致豚鼠耳蜗外毛细胞功能明显减退,这种功能减退尚不足以引起听力的明显改变。     

Dexamethasone modifies the effect of Pseudomonas aeruginosa exotoxin A on hearing

In the present study, the protective effect of dexamethasone was analysed following exposure of the cochlea to Pseudomonas aeruginosa Exotoxin A (PaExoA). Four groups of albino Sprague-Dawley rats were used. 20 microl saline was instilled through the tympanic membrane into the round window niche (group A, n = 4); 1 microg/20 microl dexamethasone sodium 21-phosphate (dexamethasone) solution was instilled (group B, n = 4); 1 microg/20 microl PaExoA solution was initially instilled followed 1 h later by 20 microl saline (group C, n = 6); and 1 microg/20 microl PaExoA solution was initially instilled followed 1 h later by 1 microg/20 microl dexamethasone solution (group D, n = 6). Frequency-specific (4, 8, 10, 12, 16 and 20 kHz) auditory brainstem responses (ABR) were used to ascertain the threshold prior to exposure and 1, 2, 3, and 5 days and 1 and 2 weeks afterwards. No threshold change was observed in groups A and B, whereas the animals in groups C and D showed some threshold elevation, that in D being smaller than that in C. There was a significant difference at the frequencies 12, 16 and 20 kHz, 2 and 5 days after exposure. The intensity-latency (I-L) curve showed that in group D the cochlear component almost disappeared at high frequency one week after exposure. Our results indicate that dexamethasone can modify the effect of PaExoA caused by non-specific inflammation.     

Determining the cause of hearing loss: differential diagnosis using a comparison of audiometric and otoacoustic emission responses

OBJECTIVE: The purpose of this study was to further investigate the possibility of developing noninvasive methods of differential diagnosis of hearing disorders through the study of experimental animals with induced lesions. In particular, it was desired to compare distortion product otoacoustic emission (DPOAE) responses and auditory brain stem response (ABR) thresholds in Mongolian gerbils having either acoustic or strial damage, using as a reference the same responses measured in a control group of normal young adult gerbils. The goal was to evaluate the potential clinical application of this approach to determining the dominant contribution to sensorineural hearing loss in individual human subjects. DESIGN: DPOAE input-output functions and ABR thresholds were measured over a wide range of stimulus frequencies for three groups: (1) a reference group of normal young adult gerbils; (2) a group in which acoustic damage had been induced 2 wk earlier; (3) a group in which damage to the stria vascularis was induced by a series of furosemide injections. The responses in the experimental groups relative to the normal means were compared to determine which combinations of responses were effective in discriminating between animals with different lesions. Three measures were evaluated in detail: the ABR threshold, the emission threshold at a criterion emission amplitude, and the emission amplitude at a high stimulus level. RESULTS: Considering cases with significant hearing loss (ABR thresholds elevated by 20 dB or more), the best method for distinguishing between the two lesions involved a two-dimensional plot comparing emission and ABR thresholds at the same stimulus frequencies. Acoustic damage cases were found in a broad region where the emission and ABR thresholds were roughly equal, whereas strial damage cases were found in a narrower region where the emission threshold was about 0.4 times the ABR threshold (both in dB). These two cases were compared with a third case introduced by definition, that is, damage to inner hair cell or neural systems resulting in an increase in audiometric threshold but no change in emission responses (e.g., auditory neuropathy). The responses for these three cases were found to lie in different regions of the two-dimensional plot comparing emission and ABR thresholds, provided only that ABR thresholds were elevated 20 dB or more. This diagram also revealed cases of preclinical acoustic damage, in which the ABR threshold was shifted less than 20 dB but where the emission threshold was significantly elevated. CONCLUSIONS: The results clearly demonstrate the possibility of developing a clinical method of noninvasive differential diagnosis of hearing loss. The method demonstrated was to add to a standard audiometric evaluation the measurement of DPOAE growth functions over the range of frequencies where these emissions were relatively easy to measure and consistent. The DPOAE stimulus frequencies were chosen to match the audiometric frequencies, and the corresponding emission and audiometric thresholds were compared on a threshold-threshold plot for each individual at a number of stimulus frequencies. Responses in different regions in this plot were found to correspond to different types of sensorineural hearing loss.     

Age-related sensitivity to cisplatin ototoxicity in gerbils.

This study was undertaken to define the developmental period of maximal sensitivity to cisplatin ototoxicity in gerbils. Five groups were established based upon post-natal age (P) at exposure to cisplatin, P10 (n = 8), P14 (n = 8), P18 (n = 6), P22 (n = 7) and P42 (n = 7). Animals were given cisplatin, 1 mg/kg/day intraperitoneal for 4 days. In the first four groups, P10, P14, P18 and P22, distortion product otoacoustic emissions were measured at 45 days of age, when responses were expected to be developmentally stable. Distortion product grams and input-output functions were measured. There was a statistically significant difference only between P14 and P42 (P<0.01). There was a significant interaction of age and frequency in the P14 group only (P<0.01). A secondary analysis compared distortion product grams of P14 animals, exposed to cisplatin, and age-matched saline-treated animals (n = 6). There was a significant treatment effect. In summary, there was an effect of age on the cisplatin ototoxicity in gerbils. Also, there was an effect of the frequency on DPOAE levels in P14 gerbils. These data support the presence of a 'sensitive' period to cisplatin ototoxicity in gerbils.     

Effects of exposure of the ear to GSM microwaves: in vivo and in vitro experimental studies

The effects of mobile phone (GSM) microwaves on the ears of guinea pigs were investigated in two in vivo experiments and one in vitro experiment. In the first experiment, three groups of eight guinea pigs had their left ear exposed for 1 h/day, 5 days/week, for 2 months, to GSM microwaves (900 MHz, GSM modulated) at specific absorption rates (SARs) of 1, 2 and 4 W/kg respectively, and a fourth group was sham-exposed. Distortion-product otoacoustic emissions (DPOAEs) were measured for each ear before exposure, at the end of the 2-month exposure period, and 2 months later. In the second experiment, the same protocol was applied to eight sham-exposed and 16 exposed guinea pigs at 4 W/kg, but the auditory brainstem response (ABR) thresholds were monitored. Repeated-measures ANOVA showed no difference in DPOAE amplitudes or in ABR thresholds between the exposed and non-exposed ears and between the sham-exposed and exposed groups. In the course of the second experiment, acute effects were also investigated by measuring once, in all animals, ABR thresholds just before and just after the 1-h exposure: no statistically significant difference was observed. In vitro, the two organs of Corti (OCs) of newborn rats (n = 15) were isolated and placed in culture. For each animal, one OC was exposed for 24–48 h to 1 W/kg GSM microwaves, and the other was sham-exposed. After 2–3 days of culture, all OCs were observed under light microscopy. They all appeared normal to naive observers at this stage of development. These results provided no evidence that microwave radiation, at the levels produced by mobile phones, caused damage to the inner ear or the auditory pathways in our experimental animals.