Lower Dose of Aminoglycoside Ototoxic Exposure Causes Presynaptic Alterations Assoicated with Hearing Loss

Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From the 14th to 28th days, the mice were maintained free of gentamicin treatment. Immunohisto-chemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses. RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory func-tion was assessed by auditory brainstem responses. The stereocilia of outer hair cells (OHCs) and IHCs was examined by scanning electron microscopy (SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day. RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28th day. Mild changes in stereocil-ia were only observed in OHCs on the 28th day. Conclusions These findings indicate that presynapse co-chlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochle-ae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.     

Effects of noise exposure on auditory brainstem response and speech-in-noise tasks: a review of the literature

Abstract

Objective: Short-term noise exposure that induces transient changes in thresholds has induced permanent cochlear synaptopathy in multiple species. Here, the literature was reviewed to gain translational insight into the relationships between noise exposure, ABR metrics, speech-in-noise performance and TTS in humans.

Design: PubMed-based literature search, retrieval and review of full-text articles. Study Sample: Peer-reviewed literature identified using PubMed search.

Results: Permanent occupational noise-induced hearing loss (NIHL) is frequently accompanied by abnormal ABR amplitude and latency. In the absence of NIHL, there are mixed results for relationships between noise exposure and ABR metrics. Interpretation of speech-in-noise deficits is difficult as both cochlear synaptopathy and outer hair cell (OHC) loss can drive deficits. Reductions in Wave I amplitude during TTS may reflect temporary OHC pathology rather than cochlear synaptopathy. Use of diverse protocols across studies reduces the ability to compare outcomes across studies.

Conclusions: Longitudinal ABR and speech-in-noise data collected using consistent protocols are needed. Although speech-in-noise testing may not reflect cochlear synaptopathy, speech-in-noise testing should be completed as part of a comprehensive test battery to provide the objective measurement of patient difficulty.     

Noise induced reversible changes of cochlear ribbon synapses contribute to temporary hearing loss in mice

Conclusion: Noise exposure can cause a decline in cochlear ribbon synapses and result in consequent hearing loss. The reduction of synaptic puncta appears reversible and may contribute to hearing restoration in mice after noise exposure. Objective: To detect whether noise induced reversible changes of cochlear ribbon synapses contribute to temporary hearing loss in C57BL/6J mice. Methods: The mice were assigned randomly to five groups and exposed to white noise at 110 dB SPL for 2 h except the control group. ABR thresholds were acquired before noise exposure (control), immediately following exposure (Day 0), or on Days 4, 7, or 14 after noise exposure. Light microscopy, scanning emission microscopy, and whole mounts examination was utilized to study whether there is morphology change of outer hair cells (OHC), inner hair cells (IHC), or spiral ganglion cells (SGN) due to the 110 dB white noise. Moreover, experimental approaches, including immunostaining and confocal microcopy, were used to detect whether ribbon synapses were the primary targets of noise-induced temporary hearing loss. Result: Exposure to 110 dB white noise for 2 h induced TTS in mice, with the maximal ABR threshold elevations seen on the 4^th day after noise exposure. There were no significant morphological changes in the cochlea. Paralleled changes of pre-synaptic ribbons in both the number and post-synaptic density (PSDs) during this noise exposure were detected. The number of pre-synaptic ribbon, post-synaptic density (PSDs), and co-localized puncta correlated with the shifts of ABR thresholds. Moreover, a complete recovery of ABR thresholds and synaptic puncta was seen on the 14^th day after the noise stimulations.     

The ototoxic interaction of styrene and noise

The interaction between noise and inhaled styrene on the structure and function of the auditory organ of the male Wistar rat was studied. The animals were exposed either to 600 ppm, 300 ppm or 100 ppm styrene (12 h/day, 5 days/week, for 4 weeks) alone or in combination with a simultaneous 100-105 dB industrial noise stimulant. Auditory sensitivity was tested by auditory brainstem audiometry at 1.0, 2.0, 4.0 and 8.0 kHz frequencies. Inner ear changes were studied by light microscopy. Exposure to 600 ppm styrene alone caused a 3 dB hearing loss only at the highest test frequency (8 kHz). Quantitative morphological analysis of cochlear hair cells (cytocochleograms) showed a severe outer hair cell (OHC) loss particularly in the third OHC row of the upper basal and lower middle coil. Exposure to noise alone caused only a mild hearing loss (2-9 dB), and only an occasional loss of OHCs (<1% missing). Exposure to the combination of noise and 600 ppm styrene caused a moderate flat hearing loss of 23-27 dB. The cytocochleograms showed a more severe damage of the OHCs than after exposure to 600 ppm styrene alone. The inner hair cells were found to be destroyed in some animals in the upper basal turn only after the combination exposure. Only in combination with noise exposure, the lower styrene concentrations (100 and 300 ppm) induced a hearing loss which was equivalent to that seen after exposure to noise alone. We conclude that: (1) There is an ototoxic interaction between styrene and noise. (2) Synergism is manifested only if styrene is applied in concentrations above the critical level (between 300 and 600 ppm in this study).     

Relation between outer hair cell loss and hearing loss in rats exposed to styrene

The relationship between outer hair cell (OHC) loss and cochlear sensitivity is still unclear, because in many animal models there exist surviving but dysfunctional OHCs and also injured/dead inner hair cells (IHC). Styrene is an ototoxic agent, which targets and destroys OHCs starting from the third row to the second and first rows depending on the exposure level. The remaining cells may be less affected. In this experiment, rats were exposed to styrene by gavage at different doses (200-800mg/kg/day) for varying periods (5 days/week for 3-12 weeks). An interesting finding was that the cochlear sensitivity was not affected in a few rats with all OHCs in the third row being destroyed by styrene. A further loss of OHCs was usually accompanied with a linear input/output (I/O) function of cochlear compound action potentials (CAP), indicating the loss of cochlear amplification. However, normal CAP amplitudes at the highest stimulation level of 90dB SPL were often observed when all OHCs were destroyed, indicating normal function of the remaining IHCs. The OHC-loss/hearing-loss relation appeared to be a sigmoid-type function. Initially, styrene-induced OHC losses (<33%) did not result in a significant threshold shift. Then CAP threshold shift increased dramatically with OHC loss from 33% to 66%. Then, CAP threshold changed less with OHC loss. The data suggest a tri-modal relationship between OHC loss and cochlear amplification. That is, under the condition that all surviving OHCs are ideally functioning, the cochlear amplifier is not affected until 33% of OHCs are absent, then the gain of the amplifier decreases proportionally with the OHC loss, and at last the amplifier may fail completely when more than 67% of OHCs are lost.     

Simultaneous exposure to ethyl benzene and noise: synergistic effects on outer hair cells.

The effects on hearing of simultaneous exposure to the ototoxic organic solvent ethyl benzene and broad-band noise were evaluated in rats. The effects of three ethyl benzene concentrations (0, 300 or 400 ppm) and three noise levels (95 or 105 dB(lin) SPL or background noise at 65 dB(lin) SPL) and all their combinations were investigated for a 5 day exposure at 8 h/day. Distortion product otoacoustic emissions and compound action potentials were affected after 105 dB noise alone, and after 105 dB noise in combination with ethyl benzene (300 and 400 ppm). However, the amount of loss for these combinations did not exceed the loss for 105 dB noise alone. Outer hair cell (OHC) loss after exposure to 300 ppm ethyl benzene was located in the third row of OHCs. At 400 ppm, the loss spread out to the second and first row of OHCs. Noise alone hardly affected the OHC counts except for a minor loss in the first row of OHCs after 105 dB SPL. Noise at 105 dB in combination with ethyl benzene at 300 and 400 ppm, however, showed OHC loss greater than the sum of the losses induced by noise and ethyl benzene alone.     

Cisplatin-induced ototoxicity: morphological evidence of spontaneous outer hair cell recovery in albino guinea pigs?

Cisplatin is frequently used in the treatment of various forms of malignancies. Its therapeutic efficacy, however, is limited by the occurrence of sensorineural hearing loss. Little is known about the course of hearing loss over longer time intervals after cessation of cisplatin administration. Infrequently, recovery of hearing has been described in animals and humans. Stengs et al. (1997) treated guinea pigs with cisplatin at a daily dose of 1.5 mg/kg for 8 consecutive days and subsequently studied cochlear function after survival times varying from 1 day to 16 weeks. Spontaneous improvement of the hair cell-related potentials (cochlear microphonics and summating potentials) was observed starting 2 weeks after cessation of treatment. In the present study we examined light microscopically the cochleas used in the study of Stengs et al. (1997). One day after cessation of cisplatin administration outer hair cell (OHC) loss in the basal cochlear turn averaged 66%. In the 1-week survival group, OHC counts were similar to those of the 1-day survival group. In the 4-week survival group, however, a relatively small loss of OHCs was found in the basal cochlear turn; OHC loss averaged only 15%. A similar loss was found after 8 weeks. In the 16-week survival group, OHC loss in the basal turn increased to 48%, but this was not statistically significant. Our histological observations are in line with the electrophysiological data from the same animals. Our findings suggest that OHCs recover from cisplatin-induced damage 1-4 weeks after treatment. However, the results do not allow a conclusion as to whether the observed recovery is due to the formation of new OHCs or to (self-)repair of damaged OHCs.     

D-methionine pre-loading reduces both noise-induced permanent threshold shift and outer hair cell loss in the chinchilla

Abstract

Objective: This study tested multiple dosing epochs of pre-loaded D-methionine (D-met) for otoprotection from noise-induced hearing loss (NIHL). Design: Auditory brainstem response (ABR) thresholds were measured at baseline, 1 day, and 21 days following a 6-hour 105 dB sound pressure level (SPL) octave band noise (OBN) exposure. Outer hair cell (OHC) counts were measured after day 21 sacrifice. Study sample: Three groups of five Chinchillas laniger each were given a 2-day regimen comprising five doses of D-met (200 mg/kg/dose) intraperitoneally (IP) starting 2, 2.5, or 3 days prior to noise exposure. A control group (n = 5) received five doses of equivalent volume saline IP starting 2.5 days prior to noise exposure. Results: ABR threshold shifts from baseline to day-21 post-noise exposure were reduced in all D-met groups versus controls, reaching significance (p < 0.05) in the 3-day group. D-met groups showed reduced OHC loss relative to controls at day-21 post-noise exposure, reaching significance (p < 0.05) at all frequency regions in the 3-day group and at the 2, 4, and 8 kHz frequency regions in the 2.5-day group. Conclusions: D-met administration in advance of noise-exposure, without further administration, significantly protects from noise-induced ABR threshold shift and OHC loss.     

The effects of acoustic environment after traumatic noise exposure on hearing and outer hair cells

Previous studies reported that exposure to non-traumatic level sounds after traumatic noise exposure reduced the degree of noise-induced hearing loss and hair cell stereocilia damage. The current study investigated the effects of a 3-day post-noise acoustic environment on the degree of noise-induced hearing loss and cochlear damage. Female chinchillas were exposed to traumatic continuous noise (4 kHz octave-band noise) at 107 dB SPL for 1 h and then placed in either an augmented acoustic environment (AAE) or deprived acoustic environment (DAE) for 3 days. The AAE group was exposed to a broad-band noise (4–20 kHz) at 80 dB SPL and the DAE animals were fit with conventional earplugs to minimize the level of acoustic stimulation. Auditory brainstem responses (ABRs) were recorded before and 3 days after the traumatic noise exposure. The AAE group showed a significantly lower average threshold shift at the frequencies of 4 and 8 kHz (p < 0.01). Correspondingly, significantly fewer missing and dying outer hair cells (OHCs) were observed in the AAE group than in the DAE group. Although the cochlear reduced and oxidized glutathione levels (GSH and GSSG, respectively) were essentially the same in two groups at day 3, significant correlations were found between GSSG levels and mean ABR threshold shift (1–16 kHz) in the AAE group; as well as GSSG and percentage of total OHC loss in the DAE group. The results suggest that post-noise acoustic environment influenced the degree of hearing loss and OHC deterioration after traumatic noise exposure.     

豚鼠冲击波负压暴露后耳蜗毛细胞损害定量观察

目的 探讨冲击波负压（blast underpressure,BUP）暴露后豚鼠耳蜗毛细胞损害特点.方法将豚鼠暴露实验性BUP 14天后处死,硝酸银染色硬铺片法计数观察耳蜗基底膜毛细胞损伤情况.结果压力峰值介于-22.4kPa和-63.3kPa之间的实验性BUP暴露后,豚鼠耳蜗外毛细胞出现了明显的病理性改变,损伤的程度以第二转最重,第二排和第三排的病变比第一排更为严重.BUP强度越高,毛细胞损害越重.各实验组动物的外毛细胞总缺失率明显高于正常对照组（P＜0.01）;重复暴露3次的动物外毛细胞缺失率明显高于暴露1次的动物（P＜0.01）.结论BUP暴露可引起明显的豚鼠耳蜗外毛细胞缺失等损害,其损害程度与负压峰值及暴露次数密切相关;毛细胞损害越重,ABR阈移也就越明显.     

The cortitoxic effects of cis-platinum in the guinea pig

Summary Cis-diammine-dichloroplatinum-II (DDP)-induced cochlear degeneration in the guinea pig was studied by complete hair-cell counting (cytocochleograms) and transmission electron microscopy. The DDP (1.5 mg/kg/day) was administrated over a period of 5–20 days. The degeneration of the organ of Corti started sporadically in almost every outer hair-cell (OHC) with a strong prevelance in the OHC 1 in the basal turn.No distinct starting point for the degeneration of the organ of Corti could be found. It seemed that the ototoxic effects of DDP are rather different from the ototoxic changes due to aminoglycoside antibiotics.This study showed that the animals with hearing loss due to DDP also had a clear loss of body weight. Perhaps DDP induces toxic effects (loss of body weight) which can amplify the ototoxic effects.Supported by grants from the Heinsius Houbolt Foundation     

Prestin gene expression in the rat cochlea following intense noise exposure

Noise-induced permanent loss of cochlear amplification was observed previously with the majority of outer hair cells (OHCs) still surviving in the cochlea and even with a normal OHC receptor potential, indicated by CM (cochlear microphonics) recording [Chen, G.D., Fechter, L.D., 2003. The relationship between noise-induced hearing loss and hair cell loss in rats. Hear. Res. 177(1-2), 81-90; Chen, G.D., Liu, Y., 2005. Mechanisms of noise-induced hearing loss potentiation by hypoxia. Hear. Res. 200, 1-9]. This study focused on effects of an intense noise exposure (10-20 kHz at a level of 110 dB SPL for 4 h) on the OHC motor protein (prestin) and structural proteins in the OHC membrane skeleton. The noise exposure significantly disrupted CM and CAP (cochlear compound action potential). The injured CM recovered after 1-week resting period. The impaired CAP at frequencies lower than the noise band also recovered. However, the CAP recovery at frequencies of the noise band stopped at a linear line one week after the noise exposure, indicating a permanent loss of cochlear amplification. Gene expression of prestin, beta-spectrin, and beta-actin was significantly up-regulated after the noise exposure. The elevated gene expression peaked at the 3rd post-exposure day and returned to baseline 4 weeks after the noise exposure. The up-regulated gene expression may be in response to injury of the proteins, which may be responsible for the loss of cochlear amplification.     

Dose and time dependent ototoxicity of aspartame in rats

Abstract

Conclusion: Low-dose administration of Aspartame (Ap) did not produce a significant ototoxic effect at the end of the 6th month. However, duration of the ototoxic effect is shortened and severity of the effect is increased as dose and duration of Ap administration is increased.

Objectives: While Ap toxicity has been studied in short- and long-term studies, its effects on hearing have not been investigated. This study was conducted to evaluate the effects of long-term consumption of Ap administered in various doses on hearing status of rats.

Methods: The study included 54 female Wistar Albino rats. Ap was given for 6 months to the rats. The groups were assigned according to levels of Ap dosage. DPOAE and ABR tests were utilized for serial hearing evaluations. Serial hearing measurement times were designed as baseline, 1st week, 2nd week, 1st, 2nd, 3rd, and 6th months.

Results: While audiological parameters deteriorated with 100?mg/kg/day dose after the 3rd month, ABR thresholds were elevated and DPOAE values were significantly decreased in 500?mg/kg/day and 1000?mg/kg/day applications after the 2nd month. In 2000?mg/kg/day and 4000?mg/kg/day applications, deteriorations in audiological parameters were detected as early as the first and second months; respectively.     

Effects of intense noise exposure on the outer hair cell plasma membrane fluidity

Outer hair cells (OHCs) play an important role in cochlear amplification via their length changes (electromotility). A noise-induced cochlear amplification loss leading to a permanent threshold shift (PTS) was observed without a significant hair cell loss in rats [Chen, G.D., Liu, Y., 2005. Mechanisms of noise-induced hearing loss potentiation by hypoxia. Hear. Res. 200, 1-9.]. Since motor proteins are inserted in the OHC lateral membrane, any change in the OHC plasma membrane may result in a loss of OHC electromotility, leading to a loss of cochlear amplification. In this study, the lateral diffusion in the OHC plasma membrane was determined in vitro in guinea pigs by fluorescent recovery after photobleaching (FRAP) after an in vivo noise exposure. The lateral diffusion in the OHC plasma membrane demonstrated a length-dependence, which increased as OHC length increased. A reduction in the lateral diffusion was observed in those OHCs with lengths of 50-70 microm after exposure to an 8-kHz octave band noise at 110 dB SPL for 3h. This membrane fluidity change was associated with the selective PTS at frequencies around 8 kHz. The reduction of the lateral diffusion in the OHC lateral wall indicated that noise could impair the micromechanics of the OHC lateral wall and might consequently impair OHC electromotility to induce threshold shift.     

一氧化氮合酶抑制剂和神经营养因子3对噪声暴露下豚鼠耳蜗的保护作用

目的观察一氧化氮合酶抑制剂——N-硝基左旋精氨酸甲酯（N^G-nitro-L-arginine methyl ester，L-NAME）和神经营养因子3（neurotrophin 3，NT3）对噪声性听力损失的保护作用。方法80只雄性杂色豚鼠按区组随机分为非噪声组（n=20）和噪声暴露组（n=60），噪声暴露组又分为生理盐水组（n=20）、L-NAME组（n=20）、L-NAME＋NT3组（n=20）。L-NAME组和L-NAME＋NT3组动物在噪声暴露（4kHz倍频程、声压级115dB，5h）之前2d和噪声暴露前30min给予L-NAME 10mg／kg（腹腔注射），生理盐水组动物给予等体积的生理盐水。NT3（10μg／ml）在噪声暴露前4d经微量渗透泵（200μl，0．5μl／h）输入到L-NAME＋NT3组动物的右侧耳蜗鼓阶，持续到噪声暴露后10d。噪声暴露前和暴露后10d测试听性脑干反应（auditory brainstem response，ABR），暴露后3d测试耳蜗组织一氧化氮（nitric oxide，NO）水平，最后一次ABR测试后计数耳蜗毛细胞的存活率。结果无噪声暴露组动物无明显的听力改变和毛细胞缺失；生理盐水组动物的ABR阈移、毛细胞缺失率及耳蜗组织NO水平均高于L-NAME组和L-NAME＋NT3组，差异有统计学意义（P值均〈0．01）；与L-NAME组相比，L-NAME＋NT3组豚鼠的ABR阈移减小，差异有统计学意义（P〈0．01），而耳蜗组织NO水平和毛细胞缺失率差异则没有统计学意义（P=0．197及P=0．095）。结论与单独给予L-NAME相比，联合使用NT3可以更大程度减轻噪声对豚鼠耳蜗的损伤。     

Establishing the standard method of cochlear implant in Rongchang pig

Conclusions: In this investigation, a large mammal, Rongchang pigs were used to successfully establish a research platform for cochlear implant study on the routine use of it in clinic.

Objective: The aim of this study was to establish a standard method of cochlear implant in a large mammal—pig.

Methods: Rongchang pigs were selected, then divided into two groups: normal-hearing group (Mitf?+/+) and mutation group with hearing loss (Mitf ?/?). Cochlear implants were used and ABR and EABR were recorded. The implanted electrodes were observed by X-ray and HE stains.

Results: The success with cochlear implant and the best electrode position could be defined in all animals, the coiling of the cochlea reached 1.5–1.75 turns. Immediately after the operation of cochlear implants, the ABR threshold of the operated ear (right) could not be derived for each frequency at 120?dB SPL. Moreover, 7 days after surgery, the low-frequency ABR threshold of the operated ear (right) could be derived partly at 100?dB SPL, but the high-frequency ABR threshold could not be derived at 120?dB SPL. Immediately or 1 week after cochlear implants, the EABR threshold was 90?CL in the Mitf?+/+?group. This was obviously lower than the 190?CL in the Mitf ?/? group.     

Effect of infrasound on cochlear damage from exposure to a 4 kHz octave band of noise

Infrasound (i.e., <20 Hz for humans; <100 Hz for chinchillas) is not audible, but exposure to high-levels of infrasound will produce large movements of cochlear fluids. We speculated that high-level infrasound might bias the basilar membrane and perhaps be able to minimize noise-induced hearing loss. Chinchillas were simultaneously exposed to a 30 Hz tone at 100 dB SPL and a 4 kHz OBN at either 108 dB SPL for 1.75 h or 86 dB SPL for 24h. For each animal, the tympanic membrane (TM) in one ear was perforated ( approximately 1 mm(2)) prior to exposure to attenuate infrasound transmission to that cochlea by about 50 dB SPL. Controls included animals that were exposed to the infrasound only or the 4 kHz OBN only. ABR threshold shifts (TSs) and DPOAE level shifts (LSs) were determined pre- and post-TM-perforation and immediately post-exposure, just before cochlear fixation. The cochleae were dehydrated, embedded in plastic, and dissected into flat preparations of the organ of Corti (OC). Each dissected segment was evaluated for losses of inner hair cells (IHCs) and outer hair cells (OHCs). For each chinchilla, the magnitude and pattern of functional and hair cell losses were compared between their right and left cochleae. The TM perforation produced no ABR TS across frequency but did produce a 10-21 dB DPOAE LS from 0.6 to 2 kHz. The infrasound exposure alone resulted in a 10-20 dB ABR TS at and below 2 kHz, no DPOAE LS and no IHC or OHC losses. Exposure to the 4 kHz OBN alone at 108 dB produced a 10-50 dB ABR TS for 0.5-12 kHz, a 10-60 dB DPOAE LS for 0.6-16 kHz and severe OHC loss in the middle of the first turn. When infrasound was present during exposure to the 4 kHz OBN at 108 dB, the functional losses and OHC losses extended much further toward the apical and basal tips of the OC than in cochleae exposed to the 4 kHz OBN alone. Exposure to only the 4 kHz OBN at 86 dB produces a 10-40 dB ABR TS for 3-12 kHz and 10-30 dB DPOAE LS for 3-8 kHz but little or no OHC loss in the middle of the first turn. No differences were found in the functional and hair-cell losses from exposure to the 4 kHz OBN at 86 dB in the presence or absence of infrasound. We hypothesize that exposure to infrasound and an intense 4 kHz OBN increases cochlear damage because the large fluid movements from infrasound cause more intermixing of cochlear fluids through the damaged reticular lamina. Simultaneous infrasound and a moderate 4 kHz OBN did not increase cochlear damage because the reticular lamina rarely breaks down during this moderate level exposure.     

Reduced expression of sialoglycoconjugates in the outer hair cell glycocalyx after systemic aminoglycoside administration

In this study we investigated the effect of systemic aminoglycoside administration on the expression of sialoglycoconjugates in the outer hair cell (OHC) glycocalyx of the adult guinea pig. Sialoglycoconjugates were visualized by means of ultrastructural lectin cytochemistry, using Limax flavus agglutinin (LFA) and wheat germ agglutinin (WGA) as probes. Labelling densities were determined for the apical membranes (including the stereocilia and stereociliary cross-links) and basolateral membranes of OHCs in the respective (basal, middle and apical) cochlear turns from animals that had been treated with gentamicin or neomycin for 5 or 15 consecutive days. Our results indicate that: (1) sialoglycoconjugate expression in the OHC glycocalyx demonstrates an intracochlear gradient decreasing towards the apical turn; (2) OHCs demonstrate a polarity in sialoglycoconjugate expression, in that the basolateral membranes contain more sialoglycoconjugates per surface area than the apical membranes; (3) aminoglycoside administration results in reduced expression of sialoglycoconjugates in the OHC glycocalyx; in this respect, basal-turn OHCs are more susceptible than those in the middle and apical turns; (4) reduction in sialoglycoconjugate expression after aminoglycoside administration is more prominent in the basolateral membranes; and (5) the difference in ototoxic potencies between gentamicin and neomycin is not reflected at the level of sialoglycoconjugate expression. The present data support our earlier hypothesis that aminoglycosides, already at an early phase of intoxication, interfere with the function of the endoplasmic reticulum and/or the Golgi apparatus, implying that these organelles play a crucial role in the initial phase of aminoglycoside-induced OHC degeneration.     

Otoacoustic emissions in full-term newborns at risk for hearing loss

Distortion product otoacoustic emissions (DPOEs) and click-evoked otoacoustic emissions (CEOEs) characteristics of the normal newborn population have been previously reported in the literature. There is little information about DPOE evaluations in the newborn population at risk for hearing loss. The authors now report the DPOE and/or CEOE data from six full-term subjects at risk for hearing loss or with highly suspected hearing loss. These subjects were less than 1 year of age and at risk for hearing loss secondary to a history of hereditary hearing loss, meningitis, hyperbilirubinemia, and ototoxic drug exposure. Audiometric evaluation included auditory brainstem responses (ABR), behavioral observation audiometry, and tympanometry. The CEOEs and DPOEs were found to be decreased or absent in the subjects with suspected hearing loss secondary to cochlear pathology; they were found to be normal in a subject with a suspected central hearing loss. This study's data suggest that otoacoustic emissions when combined with ABR can provide a frequency-specific evaluation of cochlear function and help determine the anatomic site of a pathologic lesion.     

Acute hyperfibrinogenemia impairs cochlear blood flow and hearing function in guinea pigs in vivo

Abstract

Objective: Impairment of microcirculation is a possible cause of sudden sensorineural hearing loss (SSNHL). Fibrinogen is known as a risk factor for both microvascular dysfunction and SSNHL. Therefore, the aim of this study was to investigate the effect of elevated serum levels of fibrinogen on cochlear blood flow and hearing function in vivo. Design: One group of guinea pigs received two consecutive injections of 100 mg fibrinogen while a control group received equimolar doses of albumin. Measurements of cochlear microcirculation by intravital microscopy and of hearing thresholds by auditory brainstem response (ABR) recordings were carried out before, after first and after second injection. Study sample: Ten healthy guinea pigs were randomly assigned to a treatment group or a control group of five animals each. Results: Serum fibrinogen levels were elevated after the first and second injections of fibrinogen compared to basal values and control group respectively. Increasing levels of fibrinogen were paralleled by decreasing cochlear blood flow as well as increasing hearing thresholds. Hearing threshold correlated negatively with cochlear blood flow. Conclusions: The effect of microcirculatory impairment on hearing function could be explained by a malfunction of the cochlear amplifier. Further investigation is needed to quantify cochlear potentials under elevated serum fibrinogen levels.