Susceptibility of organ of Corti with or without melanin to acoustic overstimulation]

Albino and pigmented guinea pigs were compared in terms of susceptibility to acoustic trauma. The animals were exposed to a 4 kHz pure tone of 120 dB for 60 min. N1 thresholds of CAP were measured before and after the acoustic exposure. Changes in the outer hair cell and stria vascularis were studied using SEM and TEM. After acoustic trauma, N1 thresholds were more elevated in the albino than in the pigmented guinea pigs. Also, pathological changes in the outer hair cell and stria vascularis were more severe in the albino animals. A noteworthy finding in the stria vascularis was that the melanin in intermediate cells had moved into marginal cells. This melanin migration may be possibly involved in mechanisms underlying prevention of acoustic trauma.     

杂色和白色豚鼠听反应阈及耳蜗血管纹细胞增殖活性的差异

目的研究杂色和白色成年豚鼠正常听反应阈及耳蜗血管纹细胞增殖活性的差异。方法用听觉诱发电位仪分别测定杂色和白色豚鼠40Hz听觉相关电位(40HzAERP)及听性脑干反应(ABR)阈值;用免疫组化法检测两种豚鼠耳蜗血管纹增殖细胞核抗原(PCNA)表达的差异。结果杂色和白色豚鼠耳蜗血管纹中间细胞PCNA染色均呈阳性,但前者PCNA的表达显著强于后者;两种豚鼠的听反应阈值无显著性差异。结论正常杂色和白色成年豚鼠血管纹中间细胞均具有增殖能力,但前者的增殖能力显著高于后者,不过这种差异并不造成两种豚鼠的正常听反应阈有明显差异。     

Toxic effects of cisplatin alone and in combination with gentamicin in stria vascularis of guinea pigs

The toxic effects on the stria vascularis of treatment with cisplatin alone and combined with the aminoglycoside antibiotic, gentamicin, were studied in guinea pigs. The toxicity induced in albino and pigmented guinea pigs was investigated morphologically with light and transmission electron microscopy, and functionally by brainstem-evoked response audiometry. The results of hearing thresholds were variable, ranging from no change in one ear in some of the animals to a hearing loss of 20 dB in one or both ears when treated with low-dose cisplatin alone or in combination with gentamicin. Bilateral deafness resulted from high-dose cisplatin combined with gentamicin. The combined treatment produced prominent structural damage in the stria vascularis. The results should be considered when aminoglycoside therapy is required in conjunction with cisplatin.     

Differential susceptibility to noise-induced permanent threshold shift between albino and pigmented guinea pigs

Evidence that reduced levels of cochlear melanin are associated with increased auditory sensitivity, increased levels of auditory fatigue and an increased susceptibility to noise-induced hearing loss led us to investigate the effects of noise exposure on the cochlear microphonic (CM) in albino and pigmented English shorthair guinea pigs. CMs were recorded from the round window prior to and at 90 min and 7 days after exposure to 45 min of 126 dB noise. Thresholds for the first detectable elicitation of the CM for four pure tones were determined and the output voltage of each cochlea was measured in 10 dB steps through intensity levels which produced a maximum voltage amplitude in the CM and voltage rollover. This analysis demonstrated that: albino guinea pigs displayed significantly lower auditory thresholds than did pigmented animals before exposure to noise; thresholds were elevated to comparable levels in both groups 90 min after noise exposure; pigmented guinea pigs showed a reliable recovery in CM thresholds 7 days after exposure to noise while thresholds in the albinos remained elevated to the same degree at both 90 min and 7 days after noise; 90 min after noise exposure, the maximum voltage output of albino cochleas was significantly less than that recorded from the cochleas of the pigmented guinea pigs. These results demonstrate that albino guinea pigs are more susceptible to the ototoxic effects of high intensity noise than pigmented guinea pigs. Converging evidence indicates that some aspects of cochlear function involve melanin pigment and that its absence may produce auditory abnormalities. Reduced melanin pigmentation may also contribute to such phenomena as noise-induced threshold shifts and individual differences in noise-induced hearing loss.     

Turn-specific and pigment-dependent differences in the stria vascularis of normal and gentamicin-treated albino and pigmented guinea pigs.

The aims of the present study were to determine which structures in the stria vascularis (SV) may depend upon the presence of pigmented melanocytes both for normal morphology and for the expression of gentamicin ototoxicity in the inner ear. These pigment-dependent influences were inferred through comparisons of the SV in pigmented guinea pigs and in albinos containing nonpigmented melanocytes. Results were obtained from 6 albino and 8 pigmented guinea pigs given gentamicin, and from 3 albino and 3 pigmented control animals not receiving the drug. One-month old animals received gentamicin daily (100 mg/kg) for 14 days and recovered for an additional 14 days before being prepared for electron microscopy. The SV from each of the 4 cochlear turns was analyzed using stereological point counting procedures. In control animals, differences were found in the higher cochlear turns, where volume density for the marginal cells in albinos was abnormally large (turns 3 and 4), while the volume density for intermediate cells (melanocytes) was abnormally small (turn 3). Cell volume estimates for the intermediate cells were significantly smaller in the albino than pigmented control animals in the higher cochlear turns, indicating that functional abnormalities may be found in the albino cochlea. In animals exposed to gentamicin, marginal cell volume density was reduced significantly in turn 4 of albinos, but not in any region of the pigmented inner ears. Radial area of SV and estimates of the absolute volumes for marginal cells in albinos given gentamicin also were significantly reduced in turn 1 compared to their controls; such differences were not observed in the pigmented animals. The results indicate that marginal cell size is significantly reduced in albino but not pigmented animals 14 days after gentamicin exposure, and further suggest a role of pigmented melanocytes in ameliorating gentamicin-induced cochlear damage.     

Cisplatin ototoxicity in guinea pigs with special reference to toxic effects in the stria vascularis

The toxic effects of cisplatin (cis-diamminedichloroplatinum [II]) on the organ of Corti are well established. Few and conflicting data on this drug's effects on the stria vascularis exist. The present study presents animal experiments on the toxic effects of cisplatin in the stria vascularis and in the organ of Corti. Cisplatin-induced toxicity in albino and pigmented guinea pigs was evaluated morphologically and functionally, using light and transmission electron microscopy as well as auditory brainstem-evoked potentials on the organ of Corti and the stria vascularis. The results showed variability in hearing thresholds, ranging from no change to hearing loss of 30 dB, and prominent damage in the organ of Corti and in the stria vascularis. The toxic effects to both the organ of Corti and the stria vascularis should be considered when cisplatin is used in chemotherapy.     

内耳色素对爆震性听损伤保护作用的实验观察

目的　探讨内耳色素与爆震性听损伤的关系。方法　利用耳蜗铺片、石蜡切片、透射电镜及扫描电镜观察爆震前后白化豚鼠和杂色豚鼠耳蜗形态结构的变化 ,并对爆震前后白化豚鼠和杂色豚鼠听性脑干反应(ABR)反应阈进行测定。结果　白化豚鼠的耳蜗形态损伤和听功能损伤均较杂色豚鼠严重。结论　爆震后白化豚鼠耳蜗形态学损伤及ABR反应阈的改变均较杂色豚鼠明显。提示内耳血管纹色素颗粒与爆震性内耳损伤有关 ,机理可能为色素颗粒参与调节爆震后内淋巴液中钙离子浓度的平衡及参与清除爆震后耳蜗产生的氧自由基     

Comparative anatomy of melanin pigment in the stria vascularis. Evidence for a distinction between melanocytes and intermediate cells in the cat

Although Corti in 1851 first described the presence of cochlear pigmentation in the stria vascularis (SV) of "very old" cats, modern studies have failed to find pigment consistently in the feline stria. While the variable presence of pigment in the feline SV would appear to contrast with this structure's uniform pigmentation in other mammalian species, variability in both the distribution and abundance of inner ear pigment has rarely been studied in any species. In the present study, the SV was examined light microscopically in sectioned material or whole-mounts from pigmented and albino animals of 5 species, including the cat, guinea pig, rabbit, ferret and mouse. In these species, the SV of each pigmented animal contained varying amounts of melanin pigment and none was found in the albino inner ear. Pigmented guinea pigs contained the most uniformly dense and least variable distribution of strial melanin, followed by the rabbit, mouse, ferret and cat. Several species also displayed more strial pigment apically and less basally. In cats, pigmented cells were principally located adjacent to the strial capillaries. Ultrastructural studies of the stria in pigmented cats revealed that these perivascular cells frequently contained an abundance of pigmented organelles and other structural features which allowed them to be distinguished from intermediate cells.     

Differential susceptibility to gentamicin ototoxicity between albino and pigmented guinea pigs

The known chemical affinity of melanin pigment for aminoglycoside antibiotics has led to the suggestion that higher concentrations of these drugs will bind to the pigmented inner ear and produce greater ototoxicity compared to the nonpigmented albino cochlea. Although this has provided a compelling hypothesis, results from the few investigations to address this question have been equivocal. In the present study, cochlear microphonic (CM) thresholds were recorded from albino and pigmented guinea pigs both before and two weeks after exposure for 14 consecutive days to 100 mg/Kg gentamicin. Cochleae were dissected and half-turn segments prepared for surface examination of the organ of Corti. After gentamicin exposure, threshold shifts averaged a statistically reliable 33 dB in albinos and 19 dB for the pigmented animals. Anatomical studies revealed a significant 44% mean outer hair cell loss in albinos compared to a 21% loss in the pigmented inner ears. The results showed that albinos display greater ototoxicity from gentamicin than do pigmented guinea pigs. Aminoglycosides are known to exert toxicity through interaction with polyphosphoinositides found in high concentrations in the inner ear. Cochleae in both albino and pigmented animals appear to possess significant phospholipid concentrations and bind toxic levels of these drugs independent of inner ear pigment content. However, evidence showing that melanin can inhibit aminoglycoside activity in vitro suggests that, once these drugs bind to pigmented tissue, they may undergo inactivation in a manner unavailable to the nonpigmented albino cochlea. The present results are consistent with the possibility that cochlear melanin may inhibit gentamicin activity in vivo and decrease the severity of aminoglycoside ototoxicity in the pigmented inner ear.     

Noise-induced hearing loss: the effect of melanin in the stria vascularis.

Conflicting investigations regarding the potential protective effect of melanin against noise-induced sensorineural hearing loss have suggested that eumelanin and pheomelanin may have differing effects within the stria vascularis. Three strains of C57BL/6J mice, (+/+, a/a) wild-types (dark coats/black eyes), (c2j/c2j, a/a), albinos (white coats/pink eyes), and (+/+, Ay/Ay) yellow mice (yellow coats/black eyes), were subjected to five consecutive days of broad band noise exposure at 112 dB(A) SPL for 3 h/day. Cochlear function was evaluated with auditory brainstem response audiometry to pure tones immediately pre-exposure, 5-6 h postexposure, and 14 days post-exposure. No significant difference in the degree of sensorineural hearing loss induced in the three strains of mice was identified. The eumelanin and pheomelanin content of each stria vascularis and amount of protein per stria for both mouse and guinea pig (2/NCR) were determined via high performance liquid chromatography. No pheomelanin was found in the stria of yellow mice, suggesting that coat color is not an accurate predictor of strial melanin content. The melanin content per mg of strial protein was higher in mice than in guinea pigs. A species-specific difference in melanin content does not explain the absence of a protective effect in mice.