Exposure to blast shock waves via the ear canal induces deficits in vestibular afferent function in rats

The ears are air-filled structures that are directly impacted during blast exposure. In addition to hearing loss and tinnitus, blast victims often complain of vertigo, dizziness and unsteady posture, suggesting that blast exposure induces damage to the vestibular end organs in the inner ear. However, the underlying mechanisms remain to be elucidated. In this report, single vestibular afferent activity and the vestibulo-ocular reflex (VOR) were investigated before and after exposure to blast shock waves (∼20 PSI) delivered into the left external ear canals of anesthetized rats. Single vestibular afferent activity was recorded from the superior branch of the left vestibular nerves of the blast-treated and control rats one day after blast exposure. Blast exposure reduced the spontaneous discharge rates of the otolith and canal afferents. Blast exposure also reduced the sensitivity of irregular canal afferents to sinusoidal head rotation at 0.5–2Hz. Blast exposure, however, resulted in few changes in the VOR responses to sinusoidal head rotation and translation. To the best of our knowledge, this is the first study that reports blast exposure-induced damage to vestibular afferents in an animal model. These results provide insights that may be helpful in developing biomarkers for early diagnosis of blast-induced vestibular deficits in military and civilian populations.     

Comparison of vestibular and cochlear ototoxicity from transtympanic streptomycin administration.

HYPOTHESIS: The relative dose-related cochlear and vestibular ototoxicity produced by transtympanically injected streptomycin (SM) compared to that of gentamicin (GM) was assessed. BACKGROUND: Although SM, the first aminoglycoside used transtympanically, is thought to be selectively vestibulotoxic, it has been replaced by GM in current clinical use. Little experimental data exist that directly demonstrate the relative cochlear and vestibular ototoxicity resulting from transtympanic administration of SM compared to GM. METHODS: Histologic evaluation was performed on inner ears from Mongolian gerbils to study vestibular and cochlear damage. Comparisons were made between animals receiving single (1 x SM) and five daily (5 x SM) injections of SM/Gelfoam-slurry and similarly injected and noninjected controls. These data were compared to results obtained using GM (1 x GM and 5 x GM) reported previously. RESULTS: Two weeks after injection, parallel qualitative and quantitative changes were seen in posterior cristae and cochlear sensory epithelia in the 1 x and 5 x SM injected groups, similar to those resulting from GM injections. Statistically significant decreases in number of hair cells were seen when 5 x SM injected ears were compared to 1 x SM injected ears and control ears. Increased damage was seen with increased dosage of each drug. Whenever damage was observed to the posterior crista sensory cells, damage was also seen in cochlear hair cells. CONCLUSIONS: In this model, SM and GM produced significant cochlear damage when vestibular damage occurred. These results suggest that, in the gerbil, SM and GM are ototoxic but not selectively vestibulotoxic. Increasing the number of transtympanic injections generally increases the damage to sensory hair cells in the posterior crista and the cochlea. A variation in interanimal susceptibility to ototoxic effects exists, but the amount of damage is consistent in cochlear and vestibular hair cells from the same animal. No evidence for selective vestibular ototoxicity from transtympanic SM was found.     

高脂蛋白血症前庭损害作用的研究

目的 :了解高脂蛋白血症对前庭功能的影响作用。方法 :采用眼震电图技术检查高脂蛋白血症患者前庭功能情况 ,与正常对照组进行比较分析。结果 :6 7.2 %的高脂蛋白血症患者前庭功能表现异常 ,中枢性前庭功能异常者5 6 .2 % ,外周性异常者 37.5 % ,外周和中枢性均异常者 2 8.1%。结论 :高脂蛋白血症对前庭系统中枢部分和外周部分均有损害作用 ,缺血性损害作用可能是其损害作用的主要原因     

Middle ear instillation of gentamicin and streptomycin in chinchillas: electrophysiological appraisal of selective ototoxicity

The purpose of this study was to investigate selective vestibular ototoxicity of gentamicin and streptomycin in the chinchilla model. In total, 10 chinchillas underwent left middle ear instillation of one of three agents: gentamicin, streptomycin and saline. Electrophysiological data (otoacoustic emissions (OAEs), auditory brainstem evoked response (ABRs), and ice-water electronystagmography were recorded before and after instillation. Animals were sacrificed for temporal bone studies using scanning electron microscopy. Morphological changes in the cochlear and vestibular neuroepithelia were correlated with electrophysiological changes. Widespread ipsilateral cochlear and vestibular neuroepithelial injuries were observed and correlated with loss of OAEs, ABRs and ice-water caloric response. This study provides no evidence of selective vestibular ototoxicity of gentamicin or streptomycin. Morphological damage correlates with, but precedes loss of electrophysiological parameters. Chinchillas, like other small mammals, may not be an ideal model for the study of human ototoxicity.     

实验性高脂蛋白血症前庭损害作用的形态学观察

目的：探讨高脂蛋白血症前庭损害作用的机理。方法：喂食豚鼠胆固醇、牛油１３周,建立高脂蛋白血症动物模型、观察前庭终器显微、超微结构的改变。结果：实验动物血ＬＤＬ－ＣＨ、ＨＤＬ３－ＣＨ显著升高,ＨＤＬ２－ＣＨ无明显升高。光镜和扫描电镜下,前庭终器呈非特异性损伤性改变。透射电镜下,除细胞器变性改变外,毛细胞、支持细胞、神经杯内及基膜下结缔组织中毛细血管和微血管内皮细胞中出现脂滴、毛细胞、支持细胞及神经杯内脂褐素颗粒及溶酶体残体增多。结论;除缺血性损害作用以外,高脂蛋白血症的前庭损害作用可能还与前庭组织细胞脂质代谢紊乱有关。     

Hearing and equilibrium disorders in patients with neurosyphilis

83 patients with neurosyphilis and 12 patients with latent syphilis underwent a cochleovestibular examination. Pathological changes were present in 54% of the patients with neurosyphilis. In the group of patients with latent syphilis functional changes could only be found in 25% of the patients. The greatest number of hearing disturbances occurred in persons suffering from general paresis, 65% were affected. Usually damage occurred in both ears. Specific topical diagnosis was often not possible although the results of the stapedial reflex indicated that peripheral cochlear lesions were present. In particular damage in the level of the high frequencies seemed to be prevalent. Disturbances of the vestibular system occurred in 25% of neurosyphilis patients. Most frequently lesions occurred in patients with cerebrospinal syphilis (40%). The comparison of subjective and objective symptoms of the vestibular system were very similar in most groups. As for the results presented it is suggested that a serological treponemal test should be undertaken in patients with non-specific disturbances of the vestibulo-cochlear system.     

Nitric oxide synthase and arginase expression changes in the rat perirhinal and entorhinal cortices following unilateral vestibular damage: a link to deficits in object recognition?

Previous studies have shown that peripheral vestibular damage causes long-term neurochemical changes in the hippocampus which may be related to spatial memory deficits. Since recent studies have also demonstrated deficits in non-spatial object recognition memory following vestibular lesions, the aim of the present study was to extend these investigations into the perirhinal cortex (PRC), which is known to be important for object recognition, and the related entorhinal cortex (EC). We examined the effects of unilateral vestibular deafferentation (UVD) on the expression of four enzymes associated with neuronal plasticity, neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), arginase I and arginase II (AI and II), in the rat EC and PRC using Western blotting. Tissue was collected at 10 hs, 50 hs and 2 weeks post-UVD. In the EC and PRC, nNOS protein expression decreased on the contralateral side at 2 weeks post-UVD but not before. At the same time, eNOS protein expression increased in both regions on the contralateral side. In the EC, AII protein expression increased on the ipsilateral side at 2 weeks post-UVD. In the PRC, AI increased and decreased on the contralateral and ipsilateral sides (respectively) at 2 weeks post-UVD. AII showed a bilateral increase in the PRC at 2 weeks post-UVD. These results demonstrate changes in NOS and arginase protein expression in the PRC and EC following UVD, which are unlikely to be due to the initial severity of the vestibular syndrome because they develop well after vestibular compensation has taken place. Neurochemical changes in these regions of the medial temporal lobe may be implicated in the development of object recognition deficits that contribute to cognitive dysfunction following peripheral vestibular damage.     

Immunocytochemical and stereological study of glucocorticoid receptors in rat medial vestibular nucleus neurons and the effects of unilateral vestibular deafferentation

CONCLUSION: The results of this study suggest that neither the number of medial vestibular nucleus (MVN) neurons expressing cytosolic glucocorticoid receptors nor blood corticosterone levels change significantly during the development of vestibular compensation. OBJECTIVE: Vestibular compensation is a process of partial behavioral recovery that occurs following damage to the vestibular labyrinth. It has been suggested that this compensation process might be dependent on the release of glucocorticoids such as corticosterone at the time of unilateral vestibular deafferentation (UVD) and that changes in glucocorticoid receptors in the MVN might contribute to the initiation of the compensation process. MATERIAL AND METHODS: We compared the number of MVN neurons expressing cytosolic glucocorticoid receptors in rats at 10 h and 2 weeks following UVD, and in sham and anesthetic control animals; we also measured blood corticosterone levels. RESULTS: Using immunocytochemistry and stereology, we found that the majority of MVN neurons expressed glucocorticoid receptors, but there were no significant differences in the number of glucocorticoid receptor-expressing neurons in the ipsilateral or contralateral MVNs at 10 h or 2 weeks post-UVD; furthermore, corticosterone levels did not vary significantly between the UVD and control groups.     

Pattern of hair cell loss and delayed peripheral neuron degeneration in inner ear by a high-dose intratympanic gentamicin

To gain insights into the ototoxic effects of aminoglycoside antibiotics (AmAn) and delayed peripheral ganglion neuron death in the inner ear, experimental animal models were widely used with several different approaches including AmAn systemic injections, combination treatment of AmAn and diuretics, or local application of AmAn. In these approaches, systemic AmAn treatment alone usually causes incomplete damage to hair cells in the inner ear. Co-administration of diuretic and AmAn can completely destroy the cochlear hair cells, but it is impossible to damage the vestibular system. Only the approach of AmAn local application can selectively eliminate most sensory hair cells in the inner ear. Therefore, AmAn local application is more suitable for studies for complete hair cell destructions in cochlear and vestibular system and the following delayed peripheral ganglion neuron death. In current studies, guinea pigs were unilaterally treated with a high concentration of gentamicin (GM, 40 mg/ml) through the tympanic membrane into the middle ear cavity. Auditory functions and vestibular functions were measured before and after GM treatment. The loss of hair cells and delayed degeneration of ganglion neurons in both cochlear and vestibular system were quantified 30 days or 60 days after treatment. The results showed that both auditory and vestibular functions were completely abolished after GM treatment. The sensory hair cells were totally missing in the cochlea, and severely destroyed in vestibular end-organs. The delayed spiral ganglion neuron death 60 days after the deafening procedure was over 50%. However, no obvious pathological changes were observed in vestibular ganglion neurons 60 days post-treatment. These results indicated that a high concentration of gentamycin delivered to the middle ear cavity can destroy most sensory hair cells in the inner ear that subsequently causes the delayed spiral ganglion neuron degeneration. This model might be useful for studies of hair cell regenerations, delayed degeneration of peripheral auditory neurons, and/or vestibular compensation. In addition, a potential problem of ABR recording for unilateral deafness and issues about vestibular compensation are also discussed.     

Optical recording of membrane potential in dissociated mouse vestibular ganglion cells using a voltage-sensitive dye

We investigated membrane electrophysiological features of dissociated vestibular ganglion neurons, using a voltage-sensitive dye and a multiple site optical imaging system. The neuronal nature of the cultured vestibular ganglion cells was confirmed by positive staining with the anti-neurofilament 200 kDa antibody, using immunocytochemical methods. Optical absorption of the dye which binds to the external surface of neuron membranes increased while the cells were depolarized during perfusion with 150 mM potassium solution. The relative ratio (deltaI/I) of optical absorption change was 0.23 +/- 0.08% (means +/- S.D., n = 16). These optical responses were wavelength dependent, therefore, the optical response apparently originated from the voltage-sensitive dye. Under our experimental conditions, photodynamic damage and pharmacological effects of the dye were either absent or insignificant. We therefore concluded that optical recording is a new, practical and non-invasive method to simultaneously monitor changes in membrane potential from cultured vestibular ganglion cells. Optical recording is expected to provide further insight into mechanisms of information processing by vestibular ganglion neurons.     

The effects of noise on the vestibular system

PURPOSE: Subjects with noise-induced hearing loss sometimes also complain about balance disorders, but reports of clinical series that give contradictory results are highly controversial. This study was designed to evaluate the effects of intense noise on the vestibular labyrinth, both in subjects with symmetrical hearing loss and in subjects with asymmetrical loss, and to examine the correlation between the subjects' complaints and the results of the vestibular function tests. METHODS: A total of 258 male military personnel, heavily exposed to various intense noises, were included in the study. They were divided into 2 groups according to their hearing; 134 had a symmetrical high-tone hearing loss, and 124 had asymmetrical losses. Each group was divided into 2 subgroups according to the presence or absence of vestibular complaints. All of the subjects underwent a complete audiological and electronystagmographic evaluation. RESULTS: We found that vestibular damage caused by intense noise exposure might be expressed clinically in subjects with asymmetrical hearing loss. There was a strong correlation between the subjects' complaints and the results of the vestibular function tests. There was no correlation between the severity of the hearing loss and the vestibular symptomatology and pathology. CONCLUSIONS: Subjects exposed to intense noise may have evidence of vestibular pathology only when there is an asymmetrical hearing loss. Whenever hearing loss is symmetrical, an equal damage to the vestibular system of both ears is most probably responsible for the absence of abnormal findings on the vestibular function tests. The results of this study have important medicolegal implications for individuals exposed to intense noises.     

Isosorbide delays gentamicin-induced vestibular sensory cell death

The efficacy of isosorbide for protection from vestibular sensory cell damage was investigated. The effects of isosorbide on gentamicin-induced production of nitric oxide (NO) and reactive oxygen species (ROS) were studied by means of the fluorescence indicators 4,5-diaminofluorescein diacetate and dihydrotetramethylrosamine. The effect on gentamicin-induced vestibular sensory cell damage was examined by using an in vitro LIVE/DEAD system. Isosorbide inhibited the production of both NO and ROS. Isosorbide limited the vestibular sensory cell damage caused by gentamicin. It is, therefore, suggested that isosorbide may help to treat inner ear disorders.     

Does vestibular damage cause cognitive dysfunction in humans?

For more than a decade, evidence from animal studies has suggested that damage to the vestibular system leads to deficits in spatial navigation which are indicative of impaired spatial learning and memory. More recently, direct evidence has emerged to demonstrate that humans with vestibular disorders exhibit a range of cognitive deficits that are not just spatial in nature, but also include non-spatial functions such as object recognition memory. Vestibular dysfunction has been shown to adversely affect attentional processes and increased attentional demands can worsen the postural sway associated with vestibular disorders. Recent MRI studies also show that humans with bilateral vestibular damage undergo atrophy of the hippocampus which correlates with their degree of impairment on spatial memory tasks. These results are consistent with those from animal studies and, together, suggest that humans with vestibular disorders are likely to experience cognitive dysfunction which is not necessarily related to any particular episode of vertigo or dizziness, and therefore may occur even in patients who are otherwise well compensated. These findings may be related to the observation that patients with vestibular deficits experience a high incidence of depression and anxiety disorders.     

庆大霉素对离体培养小鼠前庭终器的损害

目的：观察并建立不同浓度庆大霉素损害新出生C 57小鼠前庭各终器的离体实验模型。方法：应用前庭终器分离取材技术、前庭器官离体培养技术和组织学检查技术观察不同浓度庆大霉素对新出生C 57小鼠前庭各终器的损害。结果：庆大霉素对离体培养前庭毛细胞的损害模式是随着剂量的增加而损害加重，庆大霉素对离体培养前庭毛细胞的破坏与其在体实验的耳毒性规律基本相似。结论：囊斑微纹区和壶腹嵴顶部的毛细胞比周边区的毛细胞更易遭受庆大霉素的破坏。     

Aging effects on vestibulo-ocular responses in C57BL/6 mice: comparison with alteration in auditory function

Age-related changes in auditory function are well documented in animal models; however, this is not the case as regards vestibular function. In this study, we evaluated age-related changes in vestibulo-ocular responses in C57BL/6 mice that are considered as a model of presbycusis. The functional data were substantiated by the findings of histological analysis of vestibular and auditory peripherals. The gain in vestibulo-ocular reflex, which reflects functionality of the vestibular system, increased in an age-dependent manner until 12 weeks and exhibited limited functional loss due to aging after 24 weeks. By contrast, no alteration in the thresholds of the auditory brainstem response (ABR) was observed from 3 to 12 weeks of age; however, ABR thresholds were significantly elevated from age 24 weeks and onwards. Histological analysis demonstrated that the degeneration of auditory peripherals was closely related with functional loss due to aging. Vestibular peripherals also exhibited age-related degeneration morphologically, although age-related dysfunction was not apparent. Age-related changes in the vestibular function of C57BL/6 mice followed a different time course when compared to changes in auditory function. These findings indicate that mechanisms for age-related changes in vestibular function differ from those of auditory function.     

Inner ear damage induced by Mycobacterium fortuitum

We used electron microscopy to investigate Mycobacterium fortuitum-induced changes in the inner ears of mice. We found that the inner and outer hair cells had degenerated and disappeared in the organ of Corti. Changes in the lower turn of the cochlea were more severe than those of the upper turn while the changes of the outer hair cells were more severe than those of the inner hair cells. Disappearance, fusion and ballooning of the sensory hairs were observed in the vestibular organs. The bacterial extract also induced inner ear damage which was similar to that caused by live M. fortuitum.     

Vestibular Drop Attacks and Meniere’s Disease as Results of Otolithic Membrane Damage—A Numerical Model

Meniere’s disease (MD) is a condition of the inner ear with symptoms affecting both vestibular and hearing functions. Some patients with MD experience vestibular drop attacks (VDAs), which are violent falls caused by spurious vestibular signals from the utricle and/or saccule. Recent surgical work has shown that patients who experience VDAs also show disrupted utricular otolithic membranes. The objective of this study is to determine if otolithic membrane damage alone is sufficient to induce spurious vestibular signals, thus potentially eliciting VDAs and the vestibular dysfunction seen in patients with MD. We use a previously developed numerical model to describe the nonlinear dynamics of an array of active, elastically coupled hair cells. We then reduce the coupling strength of a selected region of the membrane to model the effects of tissue damage. As we reduce the coupling strength, we observe large and abrupt spikes in hair bundle position. As bundle displacements from the equilibrium position have been shown to lead to depolarization of the hair-cell soma and hence trigger neural activity, this spontaneous activity could elicit false detection of a vestibular signal. The results of this numerical model suggest that otolithic membrane damage alone may be sufficient to induce VDAs and the vestibular dysfunction seen in patients with MD. Future experimental work is needed to confirm these results in vitro.

     

The use of streptomycin to induce unilateral ablation of vestibular function in the rat: a preliminary report

The goal of our research is to develop a method of applying streptomycin to the middle ear so as to destroy vestibular function unilaterally while avoiding damage to auditory function. In this preliminary experiment, a total of 42 mg of streptomycin was infused continuously over a seven-day period into one middle ear cavity of seven rats, with the opposite ear serving as a control. Histologic study revealed a moderate to severe degree of vestibular neuroepithelial damage in all of the infused ears. However, significant damage also occurred in the basal turn of the cochlea in a majority of cases.     

The influence of endolymphatic sac surgery on cochlear function and structure in guinea pigs

Experimental endolymphatic sac surgery was performed in 35 guinea pigs to evaluate the changes in cochlear function and structure caused by surgical manipulations which included incising the sac, aspirating the endolymph and probing the vestibular aqueduct. The experimental data showed that the changes in the cochlear potential, the auditory reaction threshold and the cochlear morphology in some guinea pigs were induced by these manipulations, especially aspirating the endolymph or probing the vestibular aqueduct. The possible mechanisms of the cochlear impairment may be damage caused by positive or negative pressure, the change in endolymphatic environment and the secondary inner ear hydrops. The experimental findings indicate that the cochlear function and structure can be affected by surgical manipulations, especially aspirating the endolymph or probing the vestibular aqueduct. Therefore, these manipulations should be avoided during the surgical procedure.     

突发性聋与前庭神经炎的前庭损伤差异性研究

目的　通过比较研究伴有前庭损伤的突发性聋和前庭神经炎,探讨两类疾病前庭损伤的差异。方法  2016-02-25～2016-07-20解放军总医院耳鼻咽喉头颈外科眩晕诊疗中心,突发性聋组55例,其中39例伴眩晕患者;前庭神经炎组46例。前庭双温冷热试验、头脉冲试验、颈性前庭诱发肌源性电位、眼性前庭诱发肌源性电位评价及比较突发性聋及前庭神经炎两组疾病前庭损伤差异性。结果　前庭双温冷热试验突发性聋组异常率25.45%,前庭神经炎组异常率97.82%,两组比较差异有统计学意义（χ2=54.01,P＜0.001）。头脉冲试验：突发性聋组异常率9.09%,前庭神经炎组异常率32.61%,两组比较差异有统计学意义（χ2=8.72,P =0.003）。颈性前庭诱发肌源性电位突 发性聋组异常率69.10%,前庭神经炎组异常率43.47%,两组比较差异有统计学意义（χ2=6.72,P =0.010）;眼性前庭诱发肌源性电位突发性聋组异常率54.55%,前庭神经炎组异常率63.04%,两组比较差异无统计学意义（χ2=0.745,P =0.388）。结论　突发性聋与前庭神经炎两组患者前庭损伤比较,突发性聋合并眩晕者更有可能为球囊/前庭下神经受累,损伤部位更多靠近神经终末端,损伤是低频段的;前庭神经炎的前庭损伤范围大,损伤是全频段的,高位可能性更大。