Influence of body temperature on the set-up and recovery of noise-induced cochlea damage

Summary Hypothermia during exposure to noise reduced hair-cell damage which, on the contrary, was prevented from recovering by narcosis and hypothermia.Hyperthermia is apparently able to eliminate the narcosisdependent limitation of metabolism.A noise damage happens to develop by decompensating the excessively overburdened metabolism, whereas recovery seems to depend on the availability of a highly intracellular level of biological energy.Presented at the 17th Workshop on Inner Ear Biology in Stockholm, June 23–25, 1980     

Influence of thyroid state and improved hypoxia tolerance on noise-induced cochlea damage

Summary Guinea pigs were exposed to pure tone noise (2.7 kHz, 130 dB, 1 h) and cochlear microphonic potentials were measured 24 h after exposure.There is the possibility to modify the resulting noise-induced cochlea damage by regulating the function of the thyroid gland to alter the rate of metabolism. A hypofunction of the thyroid gland during sound exposure lessens, an over-function aggravates the damage.After gradual adaptation of the animals to a simulated 10,000 m altitude, the electrophysiologically demonstrable noise-induced damage was reduced. This might be explained by the greater hypoxia tolerance and perhaps additional better oxygen supply to the receptor cells.     

Scar formation following impulse noise-induced mechanical damage to the organ of Corti

The terminal stages of the healing process of the organ of Corti in the chinchilla following exposure to blast-waves at 160 dB peak SPL, were studied by scanning electron microscopy (SEM) and by surface preparation technique. Extensive lesions of the sensory epithelia consisting in the absence of the OHC's, Deiter cells and Hensen cells, were replaced by scar tissue formed by single, flat, irregularly polygonal cells, arising from the Claudius cell area sealing off the endolymphatic spaces. When the pillar cells have been destroyed the scar epithelium from the Claudius cells has reached the IHC's, which show a remarkable resistance to acoustic trauma. Their presence in a large healed area may be the only remnants of a previous sensory region. When even the IHC's are absent, the entire organ of Corti can be replaced both by Claudius cells and by inner sulcus cells covering the denuded basilar membrane without any clear morphological difference between the two cellular sources.     

Interaction of tamoxifen and noise-induced damage to the cochlea

Tamoxifen has been used extensively in the treatment of breast cancer and other neoplasms. In addition to its well-known action on estrogen receptors it is also known to acutely block chloride channels that participate in cell volume regulation. Tamoxifen's role in preventing cochlear outer hair cell (OHC) swelling in vitro suggested that OHC swelling noted following noise exposure could potentially be a therapeutic target for tamoxifen in its role as a chloride channel blocker to help prevent noise-induced hearing loss. To investigate this possibility, the effects of exposure to tamoxifen on physiologic measures of cochlear function in the presence and absence of subsequent noise exposure were studied. Male Mongolian gerbils (2-4 months old) were randomly assigned to different groups. Tamoxifen at ～10 mg/kg was administered to one of the groups. Five hours later they were exposed to a one-third octave band of noise centered at 8 kHz in a sound-isolation chamber for 30 min at 108 dB SPL. Compound action potential (CAP) thresholds and distortion product otoacoustic emission (DPOAE) levels were measured 30-35 days following noise exposure. Tamoxifen administration did not produce any changes in CAP thresholds and DPOAE levels when administered by itself in the absence of noise. Tamoxifen causes a significant increase in CAP thresholds from 8 to 15 kHz following noise exposure compared to CAP thresholds in animals exposed to noise alone. No significant differences were seen in the DPOAE levels in the f(2) = 8-15 kHz frequency range where maximum noise-induced increases in CAP thresholds were seen. Contrary to our original expectation, it is concluded that tamoxifen potentiates the degree of damage to the cochlea resulting from noise exposure.     

Low-dose,long-term caroverine administration attenuates impulse noise-induced hearing loss in the rat

Conclusion. Physiological and morphological assessments indicated that low-dose and long-term caroverine delivery might be a new approach to protect against impulse noise-induced hearing loss. Background. Although the exact mechanisms by which impulse noise causes hearing loss are still unclear, there is accumulating evidence that increased reactive oxygen species (ROS) production and excessive glutamate released from the inner hair cells lead to hair cell loss and consequently hearing loss. Caroverine is an antagonist of two glutamate receptors, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the inner ear, as well as an antioxidant. Materials and methods. In this study, caroverine was delivered subcutaneously using an osmotic pump. This kind of delivery has the advantage, via continuous, long-term and low dose drug administration, of avoiding systemic side effects. Results. It was shown that caroverine could significantly protect the cochlea against impulse noise trauma.     

Wave propagation and dispersion in the cochlea

Insight into cochlear mechanics can be obtained from semi-analytical and asymptotic solution methods of which the Liouville-Green (LG) method — in another context known as the WKB method — is the most important one. This paper describes the dispersion properties of fluid waves in general terms and develops the LG formulation on that basis. The eikonal equation of the LG method is shown to be identical to the dispersion relation in dispersive-wave theory. Consideration of the group velocity then leads to the derivation of the central LG formula as it has been used in an earlier paper on the LG method (Boer E. and Viergever M.A. (1982): Hearing Res. 8, 131–155). The formulation appears to apply as well to dissipative and active (i.e., energy-producing) systems. Of the many possible collateral subjects two are selected for a deeper discussion: amplification, concentration and expansion of energy, and the problem of reflection of cochlear waves. In the latter context, it is shown why — and under which conditions — cochlear waves are not reflected, despite the large degree of dispersion that they show. The analysis brings to light a fundamental asymmetry of the model regarding the direction of wave travel: waves travelling in the direction opposite to the normal one are likely to undergo reflection, while waves in the normal direction are not reflected.     

Deep-water waves in the cochlea

In order to obtain physical insight from a mathematical solution of the cochlear mechanics problem, a delicate balance is required between and refinements in modelling. For the study of the transition of long to short waves (deep-water waves) a closed-form solution is advantageous; this can, however, only be obtained at the cost of further simplification. In previous work the course of the impedance function z(x) was, therefore, reduced to the extreme; in the neighbourhood of the resonance location z(x) was assumed to be a linear function of x - the so-called ‘straight-line approximation’.This restriction is removed in the present paper. A ‘hyperbolical approximation’ of the impedance function z(x) is introduced and it is shown that with this function the two-dimensional cochlea model can be solved in closed form. The computation results show that, for not too large values of the damping parameters δ, the response in the neighbourhood of the resonance location is almost as well represented by the formerly used ‘straight-line approximation’ as by the ‘hyperbolic approximation’. Hence the principal aspects of cochlear resonance are well brought to light with the ‘straight-line approximation’. This implies that in the case under consideration the dominant part played by short waves is confirmed.When a larger range of x values is to be considered, the hyperbolic approximation is advantageous. The computed response functions agree better with experimental data from the literature. However, it is clear that really satisfactory agreement seems not possible with a two-dimensional model.     

Sharp vibration maximum in the cochlea without wave reflection

The recently discovered sharp vibration maximum of the basilar membrane at the best frequency is difficult to reconcile with the reflectionless traveling wave that is implied by the empirical data. The apparent paradox is resolved by representing the cochlea as a transmission line and investigating its characteristic impedance. The appropriate differential equation has been derived previously (Zwislocki, J. (1953); J. Acoust. Soc. Am. 25, 986-989). It is valid for both long and short wave lengths found in the cochlea. The investigation reveals that, in the presence of sufficiently short waves prevailing around the vibration maximum, the characteristic impedance remains practically constant, independent of the rapid variation of the impedance of the basilar membrane. Since wave reflection depends on variation of the characteristic impedance, no wave reflection should be expected. The constancy of the characteristic impedance also enhances the vibration maximum.     

噪声暴露对大鼠耳蜗碳酸酐酶活性及mRNA表达的影响

目的：探讨噪声暴露后耳蜗碳酸酐酶（CA）活性及其mRNA表达的变化。方法：选用健康白色大鼠24只,随机分为4组,1组为正常对照组,另外3组为实验组。实验组暴露在4kHz、110dBSPL窄带白噪声环境中4h／d,分别测试噪声暴露1d、1周、3周和对照组大鼠脑干反应（ABR）。采用免疫组织化学法观察耳蜗外侧壁CA的活性,RT-PCR检测大鼠耳蜗CAIImRNA的表达。结果：噪声暴露后大鼠ABR阈值较对照组显著增加;而耳CA活性及CAIImRNA的表达较对照组显著下降;随着噪声暴露时间的延长,ABR阈值增加而cA活性及CAIImRNA的表达呈下降趋势。结论：噪声刺激能降低耳蜗CA的活性及CAIImRNA的表达,CA可能参与了噪声性聋的发病机制。     

Prevention of impulse noise-induced hearing loss with antioxidants

Conclusion These findings indicate a strong protective effect of ALCAR and NAC on impulse noise-induced cochlear damage, and suggest the feasibility of using clinically available antioxidant compounds to protect the ear from acute acoustic injury. Objective Reactive oxygen species have been shown to play a significant role in noise-induced hearing loss. In the current study, the protective effects of two antioxidants, acetyl-L-carnitine (ALCAR) and N-L-acetylcysteine (NAC), were investigated in a chinchilla model of hearing loss resulting from impulse noise. It was hypothesized that pre- and post-treatment with these antioxidants would ameliorate the effects of impulse noise compared to saline-treated controls. Material and methods Eighteen animals were randomly assigned to 1 of 3 groups and exposed to impulse noise at a level of 155 dB peak SPL for 150 repetitions. ALCAR or NAC were administered twice daily (b.i.d.) for 2 days and 1 h prior to and 1 h following noise exposure, and then b.i.d. for the following 2 days. For the control group, saline was injected at the same time points. Auditory brainstem responses (ABRs) were recorded. Cochlear surface preparations were made to obtain cytocochleograms. Results Three weeks after exposure, permanent threshold shifts for the experimental groups were significantly reduced to ≈10–30 dB less than that for the control group (p<0.01). Less hair cell loss was also observed in the ALCAR and NAC groups than in the control group.     

JNK信号通道在强噪声诱导豚鼠耳蜗细胞凋亡的作用

目的：探讨强噪声对豚鼠耳蜗细胞死亡的机制及磷酸化c-Jun氨基末端激酶（JNK）信号通道在强噪声诱导耳蜗细胞凋亡的作用。方法：将实验组豚鼠暴露在4kHz窄带噪声120dBSPL噪声环境中4h,噪声刺激停止后1d、4d、14d组及对照组（每组各8只）在处死前测ABR。取每组4只豚鼠耳蜗作石蜡切片,另外4只豚鼠提取耳蜗总蛋白。脱氧核糖核甘酸末端转移酶介导的缺口末端标记技术（TUNEL）检测耳蜗凋亡细胞,免疫组织化学及WesternBlot方法检测JNK信号途径蛋白质P-JNK、P-c-Jun的表达。结果：实验组耳蜗Corti器毛细胞、血管纹和螺旋神经节细胞存在TUNEL阳性细胞,以1d组最多,逐渐减少,14d组最少,而对照组未见阳性细胞。免疫组织化学观察到实验组P-JNK、P-c-Jun有免疫反应阳性,定位于细胞核,对照组未见阳性细胞。Western Blot检测P-JNK、P-c-Jun含量在噪声刺激后迅速增高并快速活化,1d、4d达到高峰,随后逐渐下降,但在14d仍然维持较高水平。结论：强噪声可以通过诱导凋亡造成耳蜗细胞损伤,同时P-JNK标志着JNK信号途径的激活,提示JNK信号通道可能也是介导强噪声诱导豚鼠耳蜗细胞凋亡信号通道之一。     

Effects of exposure to noise on ion movement in guinea pig cochlea

Healthy guinea pigs were exposed to broad band noise at levels between 95 and 115 dBA for 7 days. A significant decrease of the sound-induced cochlear responses, together with a substantial increase of the endocochlear potential, was observed in guinea pigs exposed to noise at 105 or 115 dBA. Microsamples of the endolymph obtained from these guinea pigs showed a significant increase of K+ and Cl- concentrations and a decrease of Na+ concentration, when compared with those from control animals. The K+, Na+ and Cl- concentrations in the perilymph were not markedly affected by noise exposure. When the perilymphatic space was perfused with artificial perilymph containing 43K, 22Na or 36 Cl, the uptake of radiotracers into the endolymph showed a single exponential function of the perfusion time. When compared with rate constants in normal animals, the value of rate constant for K+ was significantly decreased in animals exposed to noise. These results indicate that ionic permeability changes of the endolymph-perilymph barrier are a significant factor in the physiological mechanisms underlying noise-induced hearing loss.     

Nitric oxide synthase inhibitor reduces noise-induced cochlear damage in guinea pigs

Conclusion. The results obtained in this study indicate that N^G-nitro-L-arginine methyl ester (L-NAME) protects cochlear damage from acoustic trauma through reducing the production of nitric oxide (NO). Objectives. This study aimed to explore whether NO synthase inhibitor L-NAME could reduce cochlear damage in acoustic trauma. Materials and methods. Seventy guinea pigs (300–350g) were divided randomly into four groups (n=20 in groups I, III, and IV; n=10 in group II). Two days consecutively and 30min before noise exposure (4kHz octave band, 115dB SPL 5h), subjects received an injection of 5ml saline/kg (groups I and III) or 10mg/kg L-NAME (groups II and IV). Sham-exposed guinea pigs were listed as groups I and II. Protection was assessed physiologically by the change in auditory brainstem response (ABR) threshold and histologically by survival of outer hair cells (OHCs). NO level of cochlear tissue was assayed 3days after noise exposure. Results. Group III showed significantly greater OHC loss, threshold shifts and NO level compared with group I and group IV. Compared with group III, noise-induced elevation in NO level in the cochlea was significantly attenuated by L-NAME (p<0.001).     

电子自旋共振技术观察急性声损伤后耳蜗自由基改变

目的:应用电子顺磁自旋共振(ESR)技术观察急性声损伤后豚鼠耳蜗自由基的变化规律.方法:将正常白毛红目豚鼠48只分为3组:A组(对照组)取6只豚鼠不给予噪声刺激,分别在检测听功能后测定自由基和硝酸银染色.B组21只豚鼠在(125±1)dB SPL稳态噪声暴露2h后分别于即刻、2h、6h,12h、24h、48h、72h施行ABR测试和ESR检测耳蜗自由基,检测方法为断头后快速取出耳蜗,液氮速冻.样品处理后放入ESR系统谐振腔中检测自由基含量.C组21只豚鼠在噪声暴露后于上述时间点检测听觉功能并取基膜行硝酸银染色观察Corti器毛细胞形态改变.结果:①正常豚鼠耳蜗中有少量自由基存在,其相对自由基值为(21.68±1.27).噪声暴露后即刻取样组自由基值明显升高,在暴露后2h达峰值(147.01±4.95)dB SPL,此后逐渐下降,至72h恢复至接近正常水平(53.12±2.57)dB SPL;②在125dB SPL的急性噪声暴露后,豚鼠的听阈明显提高,至6h达到峰值(73.89±2.41)dB SPL,直至72h仍未恢复到暴露前正常水平(50.28±1.48)dB SPL;③急性声损伤后形态学改变表现为外毛细胞纤毛紊乱、排列不规则,部分区域可见毛细胞缺失.结论:①急性噪声暴露后,豚鼠耳蜗内自由基水平明显增高,并在2h达峰值;②应用ESR技术检测耳蜗组织中自由基含量的方法具有直接、客观和灵敏的特点,ESR技术可用于某些内耳急性损伤动物模型的实验观察.     

鸟纲蜗管微血管的比较解剖学观察

目的：了解鸡内耳蜗管微血管的超微结构，为相关研究提供资料。方法：分别应用透射电镜和扫描电镜对10只成年鸡内耳蜗管微血管的超微结构进行观察。结果：鸡内耳蜗管组织中末见典型的薄壁毛细血管，基底膜中末见微血管分布；鸡耳蜗组织中的微血管管壁较厚，从内皮细胞至周边基膜问有呈交替排列的多层纤维、周细胞及其胞突；血管盖的每条皱签中都含有1条微血管，螺旋神经节内微血管与蜗管内的微血管结构相似；扫描电镜下，微血管表面周细胞胞突交织成网状。结论：鸡内耳蜗管微血管与哺乳纲动物内耳蜗管微血管的超微结构及分布有较大差别，其意义尚待进一步探讨。     

Distribution of canalicular reticulum in Deiters cells and pillar cells of gerbil cochlea

Postfixation with an osmium tetroxide-potassium ferrocyanide solution revealed in supporting cells in the organ of Corti a network of canaliculi termed canalicular reticulum (CR). In Deiters cells (DCs), the CR filled cytosol at the base of the phalanx and under plasmalemma apposed to either the outer hair cells' (HCs) basal surface or nerve terminals. From these locations the CR, accompanied by dense fibrillar substance, descended along microtubule bundles and terminated by surrounding the rosette complex in the apical cytosol. Canalicular profiles protruding from the reticulum penetrated the loose meshwork comprising the periphery of the rosette complex to contact at intervals branches of the dense trabeculae that make up the core of the complex. This arrangement disclosed a structural and presumably functional relationship between outer HCs and the CR and rosette complex. Inner pillar cells (PCs) exhibited moderately abundant to sparse profiles of CR interspersed between microtubule bundles of the microtubule stalk that connected head and foot regions. More elaborate CR extended as a network upward from the top of the microtubule stalk part way into the head body and downward into a conical expansion of the stalk at the base of the cell. Cytosol on the medial side of the basal microtubule expansion contained abundant CR which in conjunction with CR between basal microtubule bundles lay situated for possible uptake of ions or neurotransmitter released from numerous adjoining nerves. CR in outer PCs resembled that in inner PCs but appeared less prevalent in the head and foot regions and did not occur in cytosol beside the basal microtubule stalk. Characteristically small Golgi complexes accompanied the reticulum in DCs and were prevalent in the upper regions but absent in the mid and lower part of inner PCs. Short cisternae in the Golgi stacks associated with CR contrasted with the lengthier cisternae in the complexes infrequently observed in cytosol outside the microtubule stalk of inner PCs.