Cochlear Distribution of Na,K-ATPase and Corticosteroid Receptors in Two Mouse Strains with Congenital Hearing Disorders

As corticosteroid hormones, via their receptors, and Na,K-ATPase are thought to be involved in the regulation of endolymph production, two mouse models were used to investigate whether degeneration of the stria vascularis (SV) and disturbed endolymph composition are correlated with changes in the amounts and distribution of corticosteroid receptors and Na,K-ATPase in the cochlea. Both the shaker-2 mouse and the newly discovered mix mouse are deaf at birth and show vestibular dysfunction. In both mouse strains, the SV is degenerated and endolymph production is severely disturbed. In the shaker-2 mouse, using the C57Bl mouse as a normal control, immunohistochemical staining of mineraloand glucocorticoid receptors (MR and GR) and the Na,K-ATPase subunits &#102 1 , &#102 3 and &#103 1 showed a weaker reaction in all structures of the cochlea. The inner ear morphology of the mix mouse is described and compared to that of asymptomatic littermates. Immunostaining of MR, GR and the different Na,K-ATPase subunits in this mouse was considerably weaker in the SV, while staining intensities were normal in the remaining cochlea. The reduced corticosteroid receptor levels may lead to a reduction in Na,K-ATPase expression in the same tissues, although this conclusion should be treated with caution. The conclusion that reduced Na,K-ATPase levels in both mouse strains may be an important mechanism of the disturbed endolymph production is less controversial.     

Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus

This investigation consisted of a longitudinal study of the effects of congenital cytomegalovirus (CMV) infection on hearing sensitivity in 860 children with documented asymptomatic or symptomatic congenital CMV infection. Of the 651 children with asymptomatic CMV infection, 48 (7.4%) developed sensorineural hearing loss (SNHL), compared to 85 (40.7%) of the children with symptomatic CMV infection. Children in both groups experienced latent effects consisting of delayed onset of loss, threshold fluctuations, and/or progressive loss of hearing. It can be concluded that congenital CMV infection is a leading cause of SNHL in children. The late onset and progression of loss necessitates continued monitoring of hearing sensitivity in this population.     

Cochlear implantation in children with congenital cytomegalovirus infection accompanied by psycho-neurological disorders

In order to develop the method of laterofixation of the vocal cord (Ejnell's method) in cases of bilateral vocal cord paralysis, six autopsy specimens of normal larynx were obtained. We inserted traction sutures under conditions of direct visualization and studied the relationship between the direction of the traction exerted by the suture and subsequent enlargement of the glottis. When the vocal cord was pulled perpendicular to the thyroid cartilage wing, the mean glottal area was 106.2% of its area before traction. When the vocal cord was pulled perpendicular to the median line of the glottis, the mean glottal area was 112.7% of its area before traction. The latter angle of traction therefore produced more efficient enlargement of the glottis ( p < 0.05; paired t -test). Based on an anatomic study of cadaveric laryngeal regions, a formula was developed to predict at which point the needle should be placed in order to produce optimal results using Ejnell's technique. Further clinical studies will be carried out in patients to test the validity of this formula.     

Status of cochlear Na,K-ATPase in the aged SHR rat and its possible role in hearing loss

The relationship between levels of Na,K-AT-Pase isoforms was studied in the lateral walls of the cochlea in aged spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Dense staining for the enzyme's α₁ subunit was found especially in the basal turns of the cochlea, while external sulcal cells were more intensely stained in the more apical turns in both SHR and WKY rats. In contrast, staining for β₁ Na, K-ATPase was demonstrable in significant levels in the stria vascularis and suprastrial regions of the SHR rat, with involvement of the basilar suprastrial region pronounced in both strains of animals. Findings suggest a spatially defined, age-induced alteration in cochlear homeostasis with a possible consequent effect on sound perception.     

Lateral wall Na,K-ATPase and endocochlear potentials decline with age in quiet-reared gerbils.

Changes in the integrity of cochlear ion transport systems with age were examined in gerbils raised for 5-38 months in a quiet environment. Ion transport function was assessed by light microscopic immunohistochemical staining for the enzyme, Na,K-ATPase and by measurement of the endocochlear potential (EP). Small foci of strial atrophy accompanied by loss of immunostaining for Na,K-ATPase were observed in the stria vascularis of the apical and basal turns as early as 5 months of age. Cochleas from 29-38 month-old gerbils showed a loss of immunostaining for Na,K-ATPase in the stria in most of the apical turn with the degeneration extending well into the middle turn in many of the oldest ears. The extent of strial atrophy and loss of immunoreactive Na,K-ATPase in the basal turn varied considerably among the oldest cochleas. Populations of lateral wall fibrocytes (type II fibrocytes) normally rich in Na,K-ATPase exhibited a corresponding decrease in enzyme content in regions of advanced strial atrophy. The volume of immunostained stria vascularis correlated well with the magnitude of the resting EP. The results demonstrate that lateral wall ion transport systems in the gerbil cochlea degenerate as a function of age. The findings also provide good evidence for a functional relationship between the stria vascularis and the Na,K-ATPase-rich type II fibrocytes in generating and maintaining the EP.     

Na,K-ATPase expression in the mouse cochlea is not dependent on the mineralocorticoid receptor

This study was performed in order to test the hypothesis that the mineralocorticoid hormone stimulates the expression of Na,K-ATPase in the cochlea of the mouse. Immunohistochemistry was used to investigate the distribution of the mineralocorticoid receptor (MR) in the cochlea of the C57Bl/J6 mouse at different ages between gestational day 19 and postnatal day 30, and the occurrence and distribution of Na,K-ATPase in the inner ear of a mouse with a null mutation of the MR. Adult patterns of staining for MR were found as early as on gestational day 19 in the cochlea, with small changes thereafter. MR was detected in the same structures in the cochlea as Na,K-ATPase in earlier studies, where the amount of Na,K-ATPase increased after postnatal day 4. Thus there is latency between the increase of MR and the increase of Na,K-ATPase. In the cochlea of the MR deficient mouse, antibody labelling of Na,K-ATPase showed no significant difference as compared to the control wild type mouse. The hypothesis that mineralocorticoid hormone alone via MR stimulates the formation of Na,K-ATPase in the inner ear could not be confirmed by this study, and other regulating mechanisms must be considered.     

Vestibular findings in sensorineural hearing disorders. Results of caloric, oculomotor and hearing tests in 205 patients with unilateral hearing dysfunction

In 205 patients with unilateral hearing loss, 117 of cochlear and 88 of retrocochlear origin, thorough audiovestibular examinations were performed to establish the occurrence and severity of vestibular dysfunction. The results were also analysed with the aim of determining the relationships between the severity of the hearing loss, the etiology and the topical location of the hearing disorder, on the one hand, and vestibular dysfunction, recorded as reduced caloric sensitivity and occurrence of oculomotor disturbances, on the other. No correlation was found between severity of hearing loss and recordable vestibular dysfunction, in either the cochlear or retrocochlear group of patients, or in the etiological subgroups of these main groups. With respect to the relations between the topic locations of the lesions and the results of vestibular tests, distinct characteristics were observed. In the affected ears, totally extinguished caloric reactions were more than six times as frequent in the retrocochlear group as in the cochlear group and appeared as a specific but rather insensitive sign of acoustic neurinoma. Oculomotor disturbances were only exceptionally observed in patients with cochlear lesions, but were noted in nearly half of the retrocochlear group; when only those patients with lesions of the brain stem or cerebellum were considered, all were found to exhibit such disturbances. The relations between audiometric hearing test pattern, caloric sensitivity and oculomotor disturbances seem to form interesting diagnostic paradigms of great value for the topical localization of audiovestibular disorders.     

Cochlear degeneration in aged rats of four strains.

Animals with various degrees of inbreeding, some of which are albino, are frequently used in biological research. Albinos do not produce melanin and it is therefore absent from the cochlea. While the function of melanin is unknown, it has been hypothesized that it is involved in cochlear homeostasis. It is possible then, that age-related degeneration may be affected by the presence or absence of melanin. We therefore evaluated young (2-6 months old) and aged (24-36 months old) cochleas in 4 different rat strains: albino Fischer 344 and Lewis rats and pigmented Lewis-Brown Norway F1 rats and Brown Norway rats. Cochlear morphology was the same across all strains of young adult animals with the exception that the pigmented animals had small, darkly stained granules in the stria vascularis. The aged pigmented animals all had large granules as well as small ones. Degeneration of spiral ganglion cells in the apical region of the ganglion had occurred in the old animals of all strains. Strial degeneration at the apex was also present in aged animals. There was no correlation between the presence or absence of melanin and the magnitude of cochlear degenerative changes in the aged animals. The presence or absence of melanin therefore, appears to have no effect on cochlear degeneration in the aged rat cochlea.     

Cochlear developmental defect and background-dependent hearing thresholds in the Jackson circler (jc) mutant mouse

Jackson circler (jc) is a spontaneous, recessive mouse mutation that results in circling behavior and an impaired acoustic startle response. In this study, we refined the phenotypic and genetic parameters of the original jc mutation and characterized a new mutant allele, jc(2J). In open-field behavior tests, homozygous jc mutants exhibited abnormal circling and ambulatory behavior that was indistinguishable from that of phenotypically similar mutants with defects in the vestibule of the inner ear. The jc/jc and jc(2J)/jc(2J) mice had stable elevated auditory-evoked brainstem response (ABR) thresholds at the 16kHz stimulus of 88+/-9dB sound pressure levels (SPL) and 43+/-11dB SPL, respectively. Peak latencies and peak time intervals were normal in jc mutants. The jc mice showed no measurable distortion-product otoacoustic emissions (DPOAEs) above the system noise floor. In the mutant cochlea, the apical turn failed to form due to the developmental growth arrest of the cochlear duct at the level of the first turn at gestational day 13.5. In a large intrasubspecific intercross, jc localized to a 0.2cM interval at position 25cM on chromosome 10, which is homologous to the human 6q21 region. On CZECHII/Ei and CAST/Ei backgrounds jc/jc mutant hearing thresholds at the 16kHz stimulus were significantly lower than those observed on the C57BL/6J background, with means of 62+/-22dB SPL and 55+/-18dB SPL, respectively. Genome-wide linkage scans of backcross, intercross, and congenic progeny revealed a complex pattern of genetic and stochastic effects.     

Identification of 17 hearing impaired mouse strains in the TMGC ENU-mutagenesis screen

The Tennessee Mouse Genome Consortium (TMGC) employed an N-ethyl-N-nitrosourea (ENU)-mutagenesis scheme to identify mouse recessive mutants with hearing phenotypes. We employed auditory brainstem responses (ABR) to click and 8, 16, and 32 kHz stimuli and screened 285 pedigrees (1819 mice of 8–11 weeks old in various mixed genetic backgrounds) each bred to carry a homozygous ENU-induced mutation. To define mutant pedigrees, we measured 12 mice per pedigree in 2 generations and used a criterion where the mean ABR threshold per pedigree was two standard deviations above the mean of all offspring from the same parental strain. We thus identified 17 mutant pedigrees (6%), all exhibiting hearing loss at high frequencies (16 kHz) with an average threshold elevation of 30–35 dB SPL. Interestingly, four mutants showed sex-biased hearing loss and six mutants displayed wide range frequency hearing loss. Temporal bone histology revealed that six of the first nine mutants displayed cochlear morphological defects: degeneration of spiral ganglia, spiral ligament fibrocytes or inner hair cells (but not outer hair cells) mostly in basal turns. In contrast to other ENU-mutagenesis auditory screens, our screen identified high-frequency, mild and sex-biased hearing defects. Further characterization of these 17 mouse models will advance our understanding of presbycusis and noise-induced hearing loss in humans.     

先天性内耳畸形的人工耳蜗植入

目的　探讨先天性内耳畸形引起重度感音神经性聋者人工耳蜗植入的有关问题。方法　 2 0 0 1年 1月至 2 0 0 3年 4月间对内耳畸形引起极重度感音神经性聋 18例进行了人工耳蜗植入术。结果　 18例中前庭水管 11例 ,Waardenburg综合征 3例 ,Mondini畸形 3例 ,Usher综合征 1例。全部病例采用Nucleus 2 4型人工耳蜗 ,其中对前庭水管 5例采用Contour植入体 ,其余病例采用直电极植入体。术中发现前庭水管 11例开骨窗后仅有外淋巴搏动 ,但无井喷 (脑脊液漏 ) ,电极植入顺利。Waardenburg综合征 3例和Mondini畸形 3例中各有 1例伴发圆窗骨性封闭畸形。 结论　前庭水管者人工耳蜗植入手术顺利 ,术后效果与耳蜗发育正常者相同。如Mondini和CommonCavity等内耳畸形者行人工耳蜗植入时术前应准确评估畸形的程度及伴发的畸形 ,要充分估计手术难度和避免术后可能出现的脑脊液耳鼻漏及其颅内感染     

Rehabilitation of patients with hearing disorders using hearing aids and tactical hearing measures

After a brief summary of the problems of rehabilitation of hearing-impaired subjects, the optimal conditions for rehabilitation with hearing aids are presented: a) The right timing is crucial. b) Optimal provision of hearing aids must be carried out in close co-operation between the patient, the hearing aid technician and the otolaryngologist. c) Easy handling of the hearing aid and the use of attachments must be guaranteed. d) The hearing-impaired person must be fully informed as to the extent and type of hearing loss. He/she must accept the affliction and know about the possibilities of rehabilitation. The patient's motivation is a pre-requisite for all further steps. e) The patients must learn tactical measures to make optimal use of their hearing ability in relation to their environment. Hearing tactics consist of hearing training and a change in the attitude of the hearing-impaired patients themselves and their attitude towards their surroundings.     

Cochlear implants, vibrators and hearing aids in the rehabilitation of postlingual deafness

Three groups of postlingually deaf adults were formed by non-random selection. The subjects with some residual hearing were fitted with a powerful hearing aid (HA group, n = 10). The others received either a single-channel vibrotactile aid (V group, n = 8) or a single-channel intracochlear implant (CI group, n = 10). Training containing individual counselling and rehearsal in small groups was arranged. During the follow-up (CI group 2.0 yrs, V group 1.8 yrs, HA group 2.6 yrs), the subject's achievement was assessed by a repetition of audiological testing and written questionnaires. Whereas the HA group obtained the highest scores in the audiological tests, the CI group found the implant most beneficial in everyday life. No significant improvement in the test scores was observed during the follow-up. The extent of personal training, after an initial training period and motivation of the user, did not affect the test scores or the subjective evaluation.