Physiopathology of the cochlear microcirculation

Normal blood supply to the cochlea is critically important for establishing the endocochlear potential and sustaining production of endolymph. Abnormal cochlear microcirculation has long been considered an etiologic factor in noise-induced hearing loss, age-related hearing loss (presbycusis), sudden hearing loss or vestibular function, and Meniere's disease. Knowledge of the mechanisms underlying the pathophysiology of cochlear microcirculation is of fundamental clinical importance. A better understanding of cochlear blood flow (CoBF) will enable more effective management of hearing disorders resulting from aberrant blood flow. This review focuses on recent discoveries and findings related to the physiopathology of the cochlear microvasculature.     

H.E.L.P.-Apherese bei der Behandlung des Hörsturzes

Disturbances of cochlear microcirculation are among the most discussed causes of sudden sensorineural hearing loss. Increased levels of cholesterol and fibrinogen seem to act as risk factors for inner ear disorders. Fibrinogen/LDL apheresis greatly reduces the concentration of plasma fibrinogen thus leading to improved cochlear blood flow. In a retrospective case series remission rates of 152 patients suffering from sudden sensorineural hearing loss and resistant to former treatment were investigated after treatment with a single apheresis. Complete remission was reported in 11% of patients, partial remission in 43%. 37% had no change of hearing threshold and 2% reported a decrease in hearing. Rates of complete remissions decreased from 22% within the first 2 weeks after onset of hearing loss to 14% after 6 weeks. In the same period of time rates of partial remissions decreased from 33% to 13%. The present study shows that apheresis achieved complete or partial remission in 54% of patients even after unsuccessful treatment with another therapy and the therapeutic window lies by approximately 6 weeks.     

Recent advances in cochlear blood flow measurements

Changes in blood flow to the inner ear have been thought to influence or underlie a number of cochlear diseases, including some forms of noise-induced hearing loss, sudden hearing loss, and Meniere's disease. Recently, important advances have been made in two technologies for the study of cochlear blood flow. The first is in the area of vital microscopic studies of cochlear microcirculation, and the second is based on the introduction of laser technology in the form of laser Doppler flowmetry. In this report, measurements are given of changes in cochlear circulation caused by carbon dioxide breathing, intravenous phenylephrine injection, systemic hemodilution, positive end expiratory pressure, and direct electrical stimulation of the cochlea. From these changes, we observe that cochlear blood circulation responds to systemic blood pressure alterations and is subject to local flow control mechanisms. Linearity and speed of response of the laser Doppler instrumentation also are shown. These advances show promise for contributing to our knowledge of control mechanisms of inner ear blood flow and for revealing the influence of various pharmacologic agents of potential clinical value.     

Molecular mechanisms and roles of inflammatory responses on low-frequency residual hearing after cochlear implantation

Preservation of low-frequency residual hearing is very important for combined electro-acoustic stimulation after cochlear implantation.However,in clinical practice,loss of low-frequency residual hearing often occurs after cochlear implantation and its mechanisms remain unclear.Factors affecting lowfrequency residual hearing after cochlear implantation are one of the hot spots in current research.Inflammation induced by injury associated with cochlear implantation is deemed to be significant,as it may give rise to low-frequency residual hearing loss by interfering with the blood labyrinth barrier and neural synapses.Pathological changes along the pathway for low-frequency auditory signals transmission may include latent factors such as damage to neuroepithelial structures,synapses,stria vascularis and other ultrastructures.In this review,current research on mechanisms of low-frequency residual hearing loss after cochlear implantation and possible roles of inflammatory responses are summarized.     

Cochlear implants in genetic deafness

Genetic defects are one of the most important etiologies of severe to profound sensorineural hearing loss and play an important role in determining cochlear implantation outcomes. While the pathogenic mutation types of a number of deafness genes have been cloned, the pathogenesis mechanisms and their relationship to the outcomes of cochlear implantation remain a hot research area. The auditory performance is considered to be affected by the etiology of hearing loss and the number of surviving spiral ganglion cells, as well as others. Current research advances in cochlear implantation for hereditary deafness, especially the relationship among clinic-types, genotypes and outcomes of cochlear implantation, will be discussed in this review.     

Audiological features and mitochondrial DNA sequence in a large family carrying mitochondrial A1555G mutation without use of aminoglycoside

To elucidate the pathophysiological and genetic mechanisms of hearing loss associated with the homoplasmic mitochondrial A1555G mutation in the absence of aminoglycoside exposure, we conducted audiological and genetic analyses on 67 maternally related members of a large Japanese family carrying this mutation. A consistent pattern was evident in the audiograms, with features of sensory presbycusis, cochlear origin at all levels of hearing loss, and a high degree of vulnerability of outer hair cells. That the degree of hearing loss was similar in affected subjects within the same sibling group but differed between sibling groups suggests the involvement of nuclear modifier genes. Total mitochondrial DNA sequences were completely identical among subjects with various levels of hearing loss, and lacked additional pathogenic mutations. For the diagnosis of sensorineural hearing loss, the mitochondrial A1555G mutation should be considered when these features are present even in the absence of aminoglycoside exposure.     

Definition of fluctuant hearing loss.

In summary, fluctuant hearing loss is defined as a disorder of the inner ear characterized by fullness, roaring tinnitus, and fluctuations in hearing. It is believed to be caused by an inadequate absorption of endolymph from the endolymphatic sac, with or without one or more metabolic disorders, that interferes with the delicate balance between the production and absorption of endolymph and thus produces cochlear hydrops. This triad of fullness, roaring tinnitus, and fluctuant hearing loss resulting from cochlear hydrops is much more common than the quadrad of true turning vertigo, fullness, roaring tinnitus, and fluctuant hearing loss due to vestibular and cochlear hydrops known as Meniere's disease. Although patients with fluctuant hearing loss only may eventually develop vertigo as the chief complaint and then be said to have Meniere's disease, it is remarkable how many patients continue to suffer mainly from cochlear symptoms at all times. It would appear, because of the greater frequency of fluctuant hearing loss than in Meniere's disease, that the cochlear labyrinth is more susceptible to hydrops than the vestibular labyrinth. For the purposes of diagnosis and treatment it is very useful to separate patients into those with fluctuant hearing loss and those with Meniere's disease.     

Cochlear implantation in common forms of genetic deafness

Genetic factors are among the main etiologies of severe to profound hearing loss and may play an important role in cochlear implantation (CI) outcomes. While genes for common forms of deafness have been cloned, efforts to correlate the functional outcome of CIs with a genetic form of deafness carried by the patient have been largely anecdotal to date. It has been suggested that the differences in auditory performance may be explained by differences in the number of surviving spiral ganglion cells, etiology of hearing loss, and other factors. Knowledge of the specific loci and mutations involved in patients who receive cochlear implants may elucidate other factors related to CI performance. In this review article, current knowledge of cochlear implants for hereditary hearing loss will be discussed with an emphasis on relevant clinical genotype-phenotype correlations.     

Temporal bone histopathology of noise-induced hearing loss

To examine the relationship between hearing and changes in the inner ear, we investigated human temporal bone specimens from 2 patients with noise-induced hearing loss and prepared audio-cytocochleograms as described by Schuknecht et al. Patient 1 was a 50-year-old male who died of thyroid cancer and had worked at a printing house for 38 years. Patient 2 was a 58-year old male who died of maxillary sinus cancer and had worked in construction for 22 years. A pure-tone audiogram showed high-tone sensorineural hearing loss with c5-dip-type hearing disorder in both ears in Patient 1, and a high-tone abrupt form of sensorineural hearing loss in Patient 2. Pathological examination of the temporal bone revealed degeneration and disappearance of the organ of Corti at the basal turn and disappearance of cochlear neurons in both patients. Audio-cytocochleograms revealed hearing disorder consistent with the changes in the inner ear in both patients. Marked degeneration and disappearance of the organ of Corti and stria vascularis were present in patient 1. It is generally known that disorders of the organ of Corti for a long period is involved in the etiology of noise-induced hearing loss. This degeneration of the organ of Corti is produced at a basilar membrane with the maximum amplitude related to exposure to noise according to a physical and mechanical factors. Moreover, animal experiments have shown that exposure to noise decrease cochlear blood flow. In Patient 1 both the organ of Corti and the stria vascularis exhibited degeneration, suggesting that not only physical and mechanical factors but a cochlear circulatory disorder related to exposure to noise was involved in the etiology of the pathological changes in the temporal bone related to noise-induced hearing loss.     

叶酸缺乏导致小鼠听力障碍机制的实验研究

目的　阐明叶酸缺乏后小鼠听力损失的影响因素和机制,为临床诊疗提供依据。方法　两组小鼠分别以低叶酸饮食和正常叶酸饮食喂养10周。ABR听力测试。处死动物,心脏抽血检测血清同型半胱氨酸和叶酸量。观察两组小鼠耳蜗形态学变化。免疫印记法分析相关蛋白表达情况。TUNEL法检测小鼠耳蜗细胞凋亡情况。结果　分析显示叶酸缺乏组小鼠血清叶酸水平下降,同型半胱氨酸水平升高。ABR检查和耳蜗细胞凋亡数量发现叶酸缺乏组小鼠听力损失严重。免疫印迹检测揭示叶酸缺乏组小鼠比正常组耳蜗同型半胱氨酸升高50%,提示小鼠耳蜗高同型半胱氨酸血症。结论　高同型半胱氨酸血症和叶酸缺乏引发小鼠听力损失,与内耳同型半胱氨酸代谢障碍有关。     

Frequency selectivity and speech discrimination in sensorineural hearing loss

Two supposed measures of auditory frequency selectivity--the critical band (CB) in loudness summation and the psychoacoustic tuning curve (PTC), Both measured at 1 kHz--were compared with the capacity for speech discrimination in patients with various cochlear disorders and a relatively flat audiometric pattern. The CB in loudness summation was correlated neither to the degree of hearing loss nor to the speech discrimination score. In contrast, the PTC changed with increasing hearing loss in the same manner as the electrophysiological tuning curve (FTC), i.e. rapidly deteriorating beyond normal limit values when the hearing loss exceeded 30--40 dB (HL). Nearly the same dependency of the degree of the hearing loss was demonstrated for the speech discrimination score (determined in noise and after filtering of the signal) and a significant correlation was present between this score and cochlear tuning, as expressed by the PTC. It is proposed that the PTC is a more valid measure of auditory frequency selectivity than the CB in loudness summation. If this is accepted the results seem to support the hypothesis of impaired frequency selectivity as a major cause for deteriorated speech discrimination in patients with cochlear disorders.     

语后聋人工耳蜗植入者的心理健康状况分析

目的探讨重度听力损失者借助人工耳蜗重获听力后的心理健康状况及其与听力正常人群的差异。方法采用症状自评量表(symptom checklist 90,SCL-90)和艾森克人格问卷(Eysenck personality questionnaire,EPQ)对18例语后聋人工耳蜗使用者(耳蜗组)的心理健康状态及人格特质进行评估,并与45例听力正常组(对照组)进行比较。结果①SCL-90评分结果显示:耳蜗组在人际关系、焦虑、敌对、恐怖、偏执、精神病性六个因子方面的得分均明显高于对照组(P<0.01);躯体化、强迫、抑郁三个因子的得分两组间差异无统计学意义(P>0.05)。②EPQ评定结果显示:耳蜗组在人格特质的内外倾、神经质、精神质三个维度评分与对照组相当,两组差异无统计学意义(P>0.05)。结论植入人工耳蜗有利于改善重度聋患者的心理健康状况,但人工耳蜗植入者在社会交往过程中仍存在人际关系敏感、焦虑、偏执等不良心理状态,提示在进行听觉言语康复的同时,还应关注其心理和社会交往状况,以帮助其改善生活质量、回归主流社会。     

Probational treatment of sudden deafness with prostacyclin: a pilot study.

Sudden idiopathic hearing loss has occasionally been supposed to be caused by a disturbed microcirculation in the inner ear of unknown origin. Little is known about the regulation of cochlear blood flow and the effectiveness of drugs in cochlear microcirculation. Because animal experiments gave evidence that prostacyclin (PGI2) might be one biochemical substratum of local regulators in the flow of blood in the stria vascularis, 11 patients with sudden idiopathic hearing loss were treated once for 6 h with prostacyclin (10 ng/kg body weight/min) in a first open clinical trial. In most cases prostacyclin increased hearing level (mean value: 7.4 dB/frequency/day) more than a standard therapy with pentoxifylline. The substitution of PGI2 could be another indication of a rheologic disorder--whether per se or within a larger context of inflammation-like interaction--in the inner ear of patients with sudden hearing impairment.     

Effects of age on the distortion product otoacoustic emission growth functions.

Age-related hearing loss (presbycusis) is thought to result from age-related degeneration (aging) of the cochlea plus the cumulative effects of extrinsic damage (noise and other ototoxic agents) and intrinsic disorders (e.g. systemic diseases). Previous studies have implicated dysfunction of the hair cells (sensory presbycusis) as the principal mechanism of age-related hearing loss. However, recent evidence from quiet-reared gerbils suggests that cochlear aging results primarily from atrophy of the stria vascularis, which is associated with diminished endocochlear potential (EP), spiral ganglion atrophy, and a relatively flat audiometric loss, termed metabolic presbycusis. Because it is not currently possible to measure EP directly in the clinical setting, we wondered if cochlear metabolic dysfunction might be evidenced indirectly from existing clinical tests, specifically, the input-output (IO) growth function of the distortion product (DP) otoacoustic emissions in relation to behavioral hearing threshold levels (HTL). We anticipated finding discordance between the IO functions and HTL with either a greater decline with age in HTL than in IO functions if an age-related metabolic dysfunction of the cochlea was operant, or a greater loss of IO function than HTL if outer hair cell dysfunction was the dominant pathology. To address this supposition we analyzed existing auditory data from a large cohort of adults to determine the change with age in three aspects of the DP IO function: area under the curve, threshold, and slope. The analyses demonstrated a greater effect of age on HTL than on the DP IO measures. This effect supports the hypothesis that strial dysfunction is a substantive factor in cochlear aging. The etiology and mechanisms for this dysfunction are conjectural at present.     

高原作业环境对听力的影响

高原环境具有低温、低氧的特点,随着我国西部大开发战略的不断深入,许多工作人员需要从低海拔区域快速进入高海拔区域,此类人群,极易因低温、低氧而导致人体生理机能的改变,诱发心、脑、肾等多器官功能的损伤。耳蜗及听觉中枢对缺氧极为敏感,缺氧可导致耳蜗微循环障碍进而导致听力下降。听力受损则会导致作业能力下降,所以高原作业环境对听力的影响是我们不得不关注的一个问题,本文通过文献复习的方式对这一问题进行初步论述。     

Autoimmune mouse antibodies recognize multiple antigens proposed in human immune-mediated hearing loss.

HYPOTHESIS: Autoimmune diseased mice with hearing loss will have autoantibodies against the various cochlear antigens proposed in clinical autoimmune inner ear disease. BACKGROUND: Serum antibodies of patients with hearing loss recognize several proteins that are proposed as possible antigenic targets in the ear. This often leads to a clinical diagnosis of autoimmune inner ear disease, although it is not clear how these antibodies cause inner ear disease. Therefore, to better understand the relationship of autoantibodies and ear disease, an examination was made of serum autoantibodies in the MRL/MpJ-Fas(lpr) autoimmune mouse with hearing loss. Similar antibody patterns in the mouse would provide an animal model in which to investigate potential autoimmune mechanisms of this clinical ear disorder. METHODS: Sera from MRL/MpJ-Fas(lpr) autoimmune mice and normal C3H mice were tested by the enzyme-linked immunosorbent assay technique for reactivity against various reported cochlear antigens: heat shock protein 70 (bovine, human, bacterial), laminin, heparan sulfate proteoglycan, cardiolipin, and collagen types II and IV. RESULTS: The autoimmune mouse sera showed significantly greater antibody reactivity against all of the antigens when compared with normal mouse sera. CONCLUSIONS: Serum antibodies from autoimmune mice recognized several putative autoantigens reported for patients with hearing loss, suggesting that comparable antigen-antibody mechanisms might be operating. However, the recognition of multiple antigens did not identify any one as being the specific target in autoimmune hearing loss. The correlation of antibodies in the MRL/MpJ-Fas(lpr) autoimmune mouse and human studies indicates this animal model should aid further investigations into potential cochlear antigens in autoimmune hearing loss.     

Acoustic dysfunction and microcirculation in patients with diabetes mellitus

Modern electrophysiological methods (audiometry and biomicroscopy of the bulbar conjunctiva vessels) have been used in 157 patients with diabetes mellitus (DM) to study the acoustic function and microcirculation. Common vascular reactions of the eyeball and brain allow using the data of biomicroscopy of bulbar conjunctiva vessels for evaluation of cerebral hemodynamics in DM patients. DM causes hearing and microcirculatory disorders. A close correlation exists between duration of DM and disturbances in the acoustic analyzer (microcirculation). This should be considered in planning preventive and therapeutic measures in neurosensory hypoacusis in DM.     

The cochlea as an independent neuroendocrine organ: expression and possible roles of a local hypothalamic-pituitary-adrenal axis-equivalent signaling system

A key property possessed by the mammalian cochlea is its ability to dynamically alter its own sensitivity. Because hair cells and ganglion cells are prone to damage following exposure to loud sound, extant mechanisms limiting cochlear damage include modulation involving both the mechanical (via outer hair cell motility) and neural signaling (via inner hair cell-ganglion cell synapses) steps of peripheral auditory processing. Feedback systems such as that embodied by the olivocochlear system can alter sensitivity, but respond only after stimulus encoding, allowing potentially damaging sounds to impact the inner ear before sensitivity is adjusted. Less well characterized are potential cellular signaling systems involved in protection against metabolic stress and resultant damage. Although pharmacological manipulation of the olivocochlear system may hold some promise for attenuating cochlear damage, targeting this system may still allow damage to occur that does not depend on a fully functional feedback loop for its mitigation. Thus, understanding endogenous cell signaling systems involved in cochlear protection may lead to new strategies and therapies for prevention of cochlear damage and consequent hearing loss. We have recently discovered a novel cochlear signaling system that is molecularly equivalent to the classic hypothalamic-pituitary-adrenal (HPA) axis. This cochlear HPA-equivalent system functions to balance auditory sensitivity and susceptibility to noise-induced hearing loss, and also protects against cellular metabolic insults resulting from exposures to ototoxic drugs. This system may represent a local cellular response system designed to mitigate damage arising from various types of insult.     

感音神经性聋患者内耳CT表型与SLC26A4基因型关系探讨

目的 分析感音神经性聋患者内耳高分辨率螺旋CT(下简称CT)表型与SLC26A4基因致病性突变类型之间的关系,探讨前庭导水管扩大相关内耳畸形患者SLC26 A4基因检测辅助CT诊断的可行性.方法 以Sennaroglu2010分类为标准分析2 705例感音神经性聋患者内耳CT表型,并采用DNA测序的方法检测全部患者SLC26A4基因致病性突变检出率及突变类型,统计该基因突变在患者各类内耳CT表型中的分布特点,分析SLC26A4基因突变类型与CT表型之间的关系.结果 ①2 705例患者中CT诊断为内耳畸形826例(30.54％,826/2 705),其中耳蜗畸形446例:Michel畸形5例、耳蜗未发育12例、共同腔畸形6例、耳蜗发育不全畸形34例(CH-Ⅰ 9例、CH-Ⅱ 8例、CH-Ⅲ 17例)、耳蜗分隔不全畸形389例(IP-Ⅰ 22例、IP-Ⅱ 352例、IP-Ⅲ 15例);非耳蜗畸形380例(前庭导水管扩大340例,单纯前庭、半规管、内听道畸形40例);内耳CT正常1 879例.②共检出SLC26A4基因双等位基因致病性突变517例,其中纯合突变164例、复合杂合突变353例,均在前庭导水管扩大相关内耳畸形患者(IP-Ⅱ 264例,前庭导水管扩大253例)中检出,在本组前庭导水管扩大相关内耳畸形患者中检出率为74.71％ (517/692).结论 SLC26A4基因致病性突变与前庭导水管扩大相关内耳畸形密切相关,SLC26A4基因检测在前庭导水管扩大相关内耳畸形患者中可辅助CT成为诊断工具.