灯盏花素拮抗顺铂耳蜗毒性作用的实验研究

目的探讨灯盏花素对顺铂耳蜗毒性的拮抗作用。方法将豚鼠随机分成顺铂组、灯盏花素组和对照组,测试听性脑干反应阈值,并行光镜、电镜观察。结果灯盏花素组ABR阈值较顺铂组明显降低(P<0.01)。光镜及电镜下灯盏花素组的内、外毛细胞排列整齐有序,结构基本正常。结论灯盏花素可减轻顺铂的耳蜗毒性作用。     

Absence of Voltage-Dependent Compliance in High-Frequency Cochlear Outer Hair Cells

Cochlear outer hair cells are the key element in a mechanical amplification process that enhances auditory sensitivity and tuning in the mammalian inner ear. The electromotility of outer hair cells, that is, their ability to extend or contract at acoustic frequencies, is proposed to be the source of the mechanical amplification. For amplification to take place, some stiffness is required for outer hair cells to communicate force to the organ of Corti, the sensory epithelium of the inner ear. Modulation of this stiffness would be expected to have a significant effect on inner ear function. Outer hair cell compressive stiffness has recently been shown to be dependent on membrane potential, but this has only been demonstrated for cells originating in the apical, low-frequency segment of the cochlea, whereas cochlear amplification is arguably more important in the more basal high-frequency segment. The voltage-dependent compliance (the reciprocal of stiffness) of high-frequency outer hair cells was investigated by two methods in cells isolated from the basal turns of the guinea pig cochlea. In contrast to previous findings, no evidence was found for voltage-dependent changes in compliance. The results call into question the importance of outer hair cell voltage-dependent compliance as a component of cochlear amplification.     

Differential Distribution of Stem Cells in the Auditory and Vestibular Organs of the Inner Ear

The adult mammalian cochlea lacks regenerative capacity, which is the main reason for the permanence of hearing loss. Vestibular organs, in contrast, replace a small number of lost hair cells. The reason for this difference is unknown. In this work we show isolation of sphere-forming stem cells from the early postnatal organ of Corti, vestibular sensory epithelia, the spiral ganglion, and the stria vascularis. Organ of Corti and vestibular sensory epithelial stem cells give rise to cells that express multiple hair cell markers and express functional ion channels reminiscent of nascent hair cells. Spiral ganglion stem cells display features of neural stem cells and can give rise to neurons and glial cell types. We found that the ability for sphere formation in the mouse cochlea decreases about 100-fold during the second and third postnatal weeks; this decrease is substantially faster than the reduction of stem cells in vestibular organs, which maintain their stem cell population also at older ages. Coincidentally, the relative expression of developmental and progenitor cell markers in the cochlea decreases during the first 3 postnatal weeks, which is in sharp contrast to the vestibular system, where expression of progenitor cell markers remains constant or even increases during this period. Our findings indicate that the lack of regenerative capacity in the adult mammalian cochlea is either a result of an early postnatal loss of stem cells or diminishment of stem cell features of maturing cochlear cells.     

Altered Traveling Wave Propagation and Reduced Endocochlear Potential Associated with Cochlear Dysplasia in the BETA2/NeuroD1 Null Mouse

The BETA2/NeuroD1 null mouse has cochlear dysplasia. Its cochlear duct is shorter than normal, there is a lack of spiral ganglion neurons, and there is hair cell disorganization. We measured vertical movements of the tectorial membrane at acoustic frequencies in excised cochleae in response to mechanical stimulation of the stapes using laser doppler vibrometry. While tuning curve sharpness was similar between wild-type, heterozygotes, and null mice in the base, null mutants had broader tuning in the apex. At both the base and the apex, null mice had less phase lag accumulation with increasing stimulus frequency than wild-type or heterozygote mice. In vivo studies demonstrated that the null mouse lacked distortion product otoacoustic emissions, and the cochlear microphonic and endocochlear potential were found to be severely reduced. Electrically evoked otoacoustic emissions could be elicited, although the amplitudes were lower than those of wild-type mice. Cochlear cross-sections revealed an incomplete partition malformation, with fenestrations within the modiolus that connected the cochlear turns. Outer hair cells from null mice demonstrated the normal pattern of prestin expression within their lateral walls and normal FM 1-43 dye entry. Overall, these data demonstrate that while tonotopicity can exist with cochlear dysplasia, traveling wave propagation is abnormally fast. Additionally, the presence of electrically evoked otoacoustic emissions suggests that outer hair cell reverse transduction is present, although the acoustic response is shaped by the alterations in cochlear mechanics.     

Imprints of the inner sensory cell hairs on the human tectorial membrane

Summary Imprints indicating possible direct inner sensory cell hair contact with the tectorial membrane were observed in the cochlea of a 77-year-old woman under a scanning electron microscope (SEM). The imprints were seen in the lower and upper basal cochlear turns but not in the apical and middle turns. The small dot of imprints numbered from a few up to 12 and were arranged in various forms rather than straight lines. Contact between the tectorial membrane and inner and outer sensory cell hairs of the human cochlea was discussed from the SEM findings found in this case.     

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.     

Calcium gradients in inner ear endolymph

Recent studies suggest that endolymphatic hydrops resulting from the ablation of the endolymphatic duct and sac in guinea pigs may be caused by a disturbance of endolymph calcium homeostasis. A similar disturbance of calcium homeostasis could represent the underlying cause of Ménière's disease. In this study, we mapped the calcium concentrations and electrical potentials throughout the endolymphatic system in normal guinea pigs. Large concentration differences exist between different compartments, including a more than twofold increase along the length of the cochlea. The electrochemical potential for calcium (the force driving passive longitudinal calcium movement) was calculated for all the endolymphatic compartments. The results show that endolymph is extremely inhomogenous with respect to calcium potentials. On the basis of these potentials, it appears that calcium is transported into endolymph in the cochlea and out of endolymph in the saccule and utricle. The possibility that endolymphatic hydrops arises from a disturbance in longitudinal flow of calcium, rather than in longitudinal volume flow, is considered.     

Simultaneous Measurements of Ossicular Velocity and Intracochlear Pressure Leading to the Cochlear Input Impedance in Gerbil

Recent measurements of three-dimensional stapes motion in gerbil indicated that the piston component of stapes motion was the primary contributor to intracochlear pressure. In order to make a detailed correlation between stapes piston motion and intracochlear pressure behind the stapes, simultaneous pressure and motion measurements were undertaken. We found that the scala vestibuli pressure followed the piston component of the stapes velocity with high fidelity, reinforcing our previous finding that the piston motion of the stapes was the main stimulus to the cochlea. The present data allowed us to calculate cochlear input impedance and power flow into the cochlea. Both the amplitude and phase of the impedance were quite flat with frequency from 3 kHz to at least 30 kHz, with a phase that was primarily resistive. With constant stimulus pressure in the ear canal the intracochlear pressure at the stapes has been previously shown to be approximately flat with frequency through a wide range, and coupling that result with the present findings indicates that the power that flows into the cochlea is quite flat from about 3 to 30 kHz. The observed wide-band intracochlear pressure and power flow are consistent with the wide-band audiogram of the gerbil.     

豚鼠耳蜗核复合体的解剖

耳聋和听觉通路关系密切 ,对其结构和功能的研究尤为重要 ,而豚鼠的听觉特性与人的较为接近 ,本实验即对豚鼠 (ＣａｖｉａＰｏｒｃｅｌｌｒｓ)脑干耳蜗复合体(ＣｏｃｈｌｅａｒＮｕｃｌｅｕｓＣｏｍｐｌｅｘ ,ＣＮＣ)的解剖进行了研究。选用我国实验常用豚鼠 (ＣａｖｉａＰｏｒｃｅｌｌｒｓ) 2 0只 ,体重 350～ 50 0ｇ ,3～ 9月龄 ,雌雄不限。所有动物均选择听阈在 0～ 10ｄＢ。动物经活体灌注、开颅、取脑干、固定 ,修剪样本 ,从上丘平面横断 ,分别从样本的背侧、腹侧、外侧、尾侧观察ＣＮＣ的大体形态及其与邻近组织的关系。将上述样本取…     

Severe and extensive neonatal hearing loss in cats results in auditory cortex plasticity that differentiates into two regions

We examined the response characteristics of primary auditory cortex (A1) neurons in adult cats partially but extensively deafened by ototoxic drugs 2–8 days after birth. The damage evoked extensive A1 topographic map reorganization as also found by others, but a novel finding was that in the majority of cats with low‐frequency edges to the cochlear lesion, the area of reorganization segregated into two areas expressing the same novel frequency inputs but differentiated by neuronal sensitivity and responsiveness. Immediately adjacent to normal A1 is an approximately 1.2‐mm‐wide area of reorganization in which sensitivity and responsiveness to sound are similar to that in normal A1 in the same animals and in unlesioned adult animals. Extending further into deprived A1 is a more extensive area of reorganization where neurons have poorer sensitivity and responsiveness to new inputs. These two areas did not differ in response‐area bandwidth and response latency. We interpret these novel changes as the cortical consequences of severe receptor organ lesions extending to low‐frequency cochlear regions. We speculate that the two areas of A1 reorganization may reflect differences in the transcortical spatial distribution of thalamo‐cortical and horizontal intracortical connections. Qualitatively similar changes in response properties have been seen after retinal lesions producing large areas of visual cortical reorganization, suggesting they might be a general consequence of receptor lesions that deprive large regions of cortex of normal input. These effects may have perceptual implications for the use of cochlear implants in patients with residual low‐frequency hearing.