Vestibular and cochlear ototoxicity of topical antiseptics assessed by evoked potentials

OBJECTIVES/HYPOTHESIS: To evaluate and compare the effect of chlorhexidine gluconate, povidoneiodine, and alcohol-three antiseptics used before ear surgery-on the function of the vestibular and cochlear parts of the sand rat's inner ear. The assessment of damage is based on the recording of vestibular evoked potentials (VsEPs) and auditory brainstem response (ABR). STUDY DESIGN: Prospective controlled animal study. METHODS: Fat sand rats were randomly assigned to five different groups, each receiving topical application of a different agent: saline (control), gentamicin (ototoxic control), chlorhexidine, povidone-iodine, and alcohol. Right-side total labyrinthectomy was performed, and a polyethylene tube was inserted into the left (contralateral) middle ear. After baseline recordings were taken of VsEPs and ABR, each animal received five consecutive daily applications of the specific agent into the left middle ear. Three days after the fifth application, evoked potential recordings (VsEPs and ABRs) were repeated and compared with baseline measurements. RESULTS: Administration of saline affected neither VsEPs nor ABR. In contrast, as expected, neither of these responses could be recorded after gentamicin application. After application of chlorhexidine all waves disappeared in all sand rats. Alcohol caused the waves to disappear in some of the animals only. Povidone-iodine did not affect VsEP recordings and had only a small effect on ABR. CONCLUSIONS: Chlorhexidine and alcohol had a clear toxic effect on the vestibular and cochlear function of the inner ear of the sand rat, whereas povidone-iodine did not. Thus, taking into consideration that this is an animal study, it appears that povidone-iodine might be preferable to the other agents tested in disinfecting ears with a perforated tympanic membrane.     

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.     

Assessment of vestibular ototoxicity of ear drops by recording of vestibular evoked potentials to acceleration impulses

INTRODUCTION: The cochlear ototoxicity of several ear drops is well documented in the literature, but very few studies exist on the vestibular ototoxicity of these topical drugs. GOAL OF STUDY: To develop an animal model for the assessment of the vestibular ototoxicity of ear drops. MATERIALS AND METHODS: Two animal groups, consisting of five fat sand rats (FSRs) each, underwent unilateral labyrinthectomy. Normal saline was topically applied into the middle ear cavity of rats in the first group for 7 days (control group). Rats in the second group were treated in the same way by topical gentamicin solution. Cochlear function was assessed by the recording of auditory evoked potential (ABPs) thresholds, and vestibular function was assessed by the recording of vestibular evoked potentials (VsEPs) to angular accelerations. RESULTS: In the control group, except for the amplitude of the first wave, there was no significant difference in the VsEPs recorded before and after topical application. In the gentamicin group, VsEPs could not be recorded after 7 days, and ABPs were recorded in one case only, with a threshold of 100 dB sound pressure level (SPL). CONCLUSION: VsEPs seem to be a reliable measure for evaluating the vestibular ototoxicity of topical ear drops.     

Inner ear changes with intracochlear gentamicin administration in Guinea pigs

OBJECTIVES/HYPOTHESIS: Transtympanic administration of gentamicin is reported to be a useful treatment for vertigo in such conditions as Meniere's disease, and determining appropriate clinical dosage of gentamicin is difficult. The authors examined the relation between gentamicin dosages and inner ear function in guinea pigs. STUDY DESIGN: This study is a basic science project designed to examine cochlear and vestibular function in animal models. METHODS: Various concentrations of gentamicin solution were infused into the right inner ear of guinea pigs by osmotic pumps. Caloric nystagmus as a marker of vestibular function and the change in auditory brainstem response (ABR) threshold as a marker of cochlear function were observed. RESULTS: After 14 days of treatment, high gentamicin concentrations of 40 mg/mL caused canal paralysis and a rapid shift in ABR threshold. Animals exposed to low gentamicin concentrations of 4 mg/mL showed no obvious change in either vestibular or cochlear function. Animals exposed to moderate gentamicin concentrations of 12 mg/mL showed a moderate shift in ABR threshold and caloric malfunction. Histopathological examination revealed that after 14 days of treatment with 40 mg/mL gentamicin, severe cytoplasmic damage occurred in both vestibular and cochlear end organs. In animals treated with 12 mg/mL gentamicin, hair cells remained in the cochlear third turn and ampulla of the lateral semicircular canal. CONCLUSION: The authors established an animal model that showed the moderate damage of inner ear with moderate-dose gentamicin. The study results indicated that the appropriate administration of gentamicin could establish a stable effect on the inner ear. It may be important to select the protocol that delivers a stable dosage of gentamicin to treat patients with Meniere's disease safely and effectively.     

Bone-conducted vestibular evoked myogenic potentials in patients with congenital atresia of the external auditory canal

OBJECTIVE: The purpose of this study was to determine whether vestibular evoked myogenic potentials from the sternocleidomastoid muscle in response to bone-conducted clicks and short tone-bursts can be used to assess vestibular apparatus function in patients with conductive hearing problems, particularly bilateral external auditory canal atresia. DESIGN: Evoked-potential responses to bone-conducted auditory stimuli were recorded from the sternocleidomastoid muscle of 15 patients (11 male and four female, aged 4--20 years) with congenital bilateral atresia of the external auditory canal, with or without the middle ear anomalies. SETTING: This study was conducted in the outpatient clinic of the Tokyo University Hospital, Department of Otolaryngology, University of Tokyo. INTERVENTION: Diagnostic. OUTCOME MEASURES: Bone-conducted vestibular evoked myogenic potentials in response to clicks and short tone-bursts were recorded with surface electrodes over both sternocleidomastoids in each patient. RESULTS: In all patients, bone-conducted clicks and short tone-bursts evoked larger biphasic responses from the sternocleidomastoid ipsilateral to the stimulated ear. Short tone-bursts evoked vestibular evoked myogenic potentials with higher amplitude and better waveform morphology than clicks at the same subjective intensity. CONCLUSION: Loud auditory stimuli delivered by bone conduction can evoke myogenic potentials from the sternocleidomastoid. This method is a noninvasive, rapid, and convenient test for investigating the vestibular system function in patients with bilateral external auditory canal atresia, with or without the middle ear anomalies.     

Brainstem responses to electrical stimulation of cochlea

We performed a brainstem evoked response (BSER) study to evaluate the extent to which electrical stimulation of the cochlea was conducted centrally by facial, vestibular, and cochlear nerves. Short-term experiments were performed in three monkeys: via a postauricular approach to the round window, a molded Silastic multielectrode prosthesis was placed in the scala tympani. The BSER was recorded to threshold and suprathreshold biphasic electrical pulses delivered to the implant electrodes. A middle cranial fossa dissection was then carried out, exposing the nerves of the internal auditory canal from above. Facial and vestibular neurotomy had no significant effect on BSER, while cochlear nerve section abolished the response. In one animal, blunt pressure on the cochlear nerve caused a reversible loss of electrically evoked BSER. Electrically evoked BSER probably depends on propagated impulses in the cochlear nerve.     

水杨酸钠中耳灌注对庆大霉素耳毒性的防护作用

目的 观察水杨酸钠经中耳局部灌注给药对庆大霉素耳毒性的防护作用。方法 24只健康杂色豚鼠均接受圆窗置管术，然后随机分成3组：Ⅰ组为生理盐水对照组；Ⅱ组为庆大霉素组，腹腔注射庆大霉素，经听泡灌注生理盐水；Ⅲ组为庆大霉素加水杨酸钠组，腹腔注射庆大霉素，经听泡灌注水杨酸钠。观察各组给药前后听性脑干反应阈的变化和给药后4周毛细胞损失情况。结果 听泡置管术后ABR反应阈无明显改变；给药后2周和4周，庆大霉素组ABR反应阈较庆大霉素加水杨酸组显著增高（P〈0．01），对照组ABR反应阈无显著变化。耳蜗铺片、毛细胞计数显示庆大霉素组外毛细胞严重缺失，以底回最明显，庆大霉素加水杨酸钠组外毛细胞损失较庆大霉素组轻（P〈0．05）。对照组无明显外毛细胞缺失。结论 水杨酸钠经中耳局部给药途径可减轻庆大霉素所致听功能损害和毛细胞缺失，可在一定程度上有效预防庆大霉素的耳毒性。     

Intraoperative monitoring with transtympanic electrocochleography]

Transtympanic electrocochleography (ECoG) enables auditory evoked potentials to be recorded directly from the peripheral organ, and ECoG recordings can be used as a routine during operations. Examples of cochlear and eighth nerve monitoring in middle ear, inner ear, and cerebellopontine angle surgery are given. This monitoring tool provides a continuous feedback to the surgeon of the effects of the operation on the cochlea and the auditory pathway.     

泊洛沙姆407局部灌注对豚鼠中耳及内耳的影响

目的观察泊洛沙姆407在豚鼠体内的生物降解与排出过程，以及对听泡结构及功能的影响。方法10只健康豚鼠右侧圆窗龛灌注100μl 20％泊洛沙姆407原位凝胶作为实验组，左侧灌注生理盐水作为对照组，另取2只豚鼠不予处理作为阴性对照。灌注前及灌注后第3、7、14、28及49天行听性脑干反应（auditory brainstem response，ABR）检测，每次检测后处死2只动物，取出听泡，固定，石蜡包埋连续切片，观察凝胶在中耳腔内的生物降解情况以及对中耳腔黏膜、圆窗膜、耳蜗和前庭终器结构的影响。结果圆窗龛灌注泊洛沙姆407凝胶后ABR阈值较灌注前有所提高，但在第49天恢复至灌注前水平。第49天时凝胶基本完全降解或排出，光镜下残留少量絮状物，内含少量炎性细胞。凝胶灌注对中耳腔黏膜、圆窗膜、耳蜗及前庭终器结构均无明显影响。结论泊洛沙姆407凝胶在听泡内通过生物降解和经咽鼓管排出两种形式清除，对听泡组织无明显致炎作用，对ABR阈值有暂时性影响，但未见耳蜗及前庭终器功能和结构有不可逆性损伤。     

Effect of intratympanic application of aminoglycosides on click-evoked myogenic potentials in Guinea pigs

OBJECTIVES: Although numerous studies have identified damage to the cochlear and vestibular end organs as the primary site of aminoglycoside-induced ototoxicity, the effect on the saccule remains poorly understood, possibly due to lack of monitoring saccular function in experimental animals. Therefore, this study applied three kinds of aminoglycosides into the tympanic space of guinea pigs to examine their toxic impact on the saccule by way of click-evoked myogenic potential test coupled with morphologic assessment. DESIGN: Albino guinea pigs were treated with saline, gentamicin, tobramycin, or amikacin, with 10 animals assigned to each group. Each compound was injected directly overlying but not through the round window membrane on the left ear, with the right ear serving as a control. One week after injection, each animal underwent auditory brain stem response, caloric test, and click-evoked myogenic potential test. Animals were then killed for morphologic assessment through the use of light and electron microscopic examinations. RESULTS: The animals treated with saline, gentamicin, tobramycin, or amikacin exhibited abnormal auditory brain stem response in 0%, 30%, 100%, and 30% of cases; abnormal caloric responses were found in 0%, 100%, 40%, and 40% of cases; absent click-evoked myogenic potentials were found in 0%, 100%, 30%, and 40% of cases, respectively. Gentamicin and other groups differed significantly in abnormal rates of caloric responses and click-evoked myogenic potentials. Morphologic study of the gentamicin-treated animals confirmed that the absence of click-evoked myogenic potential originated from the lesion in the saccular macula. CONCLUSIONS: Gentamicin represents the dominant susceptibility of aminoglycoside-induced vestibulotoxicity for eliminating both semicircular canal and saccular functions. This study further confirms the findings of human studies in which the caloric and vestibular evoked myogenic potentials responses were monitored to assess the abolition of vestibular function in patients treated with intratympanic gentamicin injection.     

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

OBJECTIVE: To determine selective cochlear and vestibular ototoxicity of two aminoglycoside antibiotics (gentamicin and streptomycin) in the chinchilla model. Middle ear application of these agents mirrors the clinical practice of chemical vestibular ablation used in Meniere's disease. BACKGROUND: Middle ear instillation of gentamicin or streptomycin has become a popular form of vestibular ablative treatment for disabling Meniere's disease. The vestibular selectivity of these two drugs applied in this fashion has clinical support but is not fully established in humans. Our understanding in this regard has largely been limited to animal models exposed to systemic infusion of aminoglycosides. METHOD: Ten chinchillas underwent left middle ear instillation of one of three agents using variable dosing schedules: gentamicin (n = 6), streptomycin (n = 2), and saline (n = 2) as control. Animals were sacrificed for temporal bone studies using scanning electron microscopy. Morphologic changes in the cochlear and vestibular neuroepithelia were identified. RESULTS: Widespread cochlear and vestibular neuroepithelial injuries were observed with both gentamicin and streptomycin. Contralateral ototoxicity was variable and not related to the total dose of drug delivered. The effect of these two aminoglycosides on the dark cells of the vestibular system appeared negligible. CONCLUSION: We were unable to confirm the selective damage of vestibular end-organ in the chinchilla by either gentamicin or streptomycin, a phenomenon that is generally perceived to occur in humans. Chinchillas, like other small mammals, may not be an ideal model for the study of human ototoxicity.     

Combined administration of kanamycin and furosemide does not result in loss of vestibular function in Guinea pigs

Aminoglycoside antibiotics are known to damage the vestibular and auditory sensory epithelia. Although loop diuretics enhance the cochleotoxic effect of aminoglycosides, it is not known whether concomitant administration of an aminoglycoside and a loop diuretic affects the vestibular system. The aim of our study was to investigate the effect of co-administration of kanamycin and furosemide upon the otolith organs and to compare it to the known vestibulotoxic effect of gentamicin. Five guinea pigs were injected with a single dose of both kanamycin (400 mg/kg, s.c.) and furosemide (100 mg/kg, i.v.), 5 animals received gentamicin (100 mg/kg, i.p.) for 10 days, and 5 untreated animals served as controls. After 7 days, vestibular function was assessed by measuring vestibular short-latency evoked potentials (VsEPs) to linear acceleration stimuli and cochlear function by auditory brainstem responses (ABRs) to clicks. Hair cell densities were determined in phalloidin-stained whole mounts of the utricles and saccules, and in midmodiolar sections of resin-embedded cochleae. Co-administration of kanamycin and furosemide had no significant effect on VsEPs and hair cell densities in the utricles and saccules were not reduced. ABR thresholds were increased to a great extent (by ～60 dB), and histologically a severe loss of cochlear hair cells was observed. The effect of gentamicin, both on vestibular and cochlear function, was just the opposite. VsEP thresholds to horizontal stimulation were elevated and suprathreshold amplitudes showed a decrease, whereas cochlear function was not reduced. With this protocol, we have a tool to selectively induce cochlear or vestibular damage, which may be of interest to researchers and clinicians alike.     

Indications of a differentiated regulation of sound transmission by the middle ear muscles of the rat

Measurement of the middle ear muscle reflex is an important tool in audiologic examination; however, the precise function of the tensor tympani and stapedius muscle is not fully understood. The function of the middle ear muscles in speech discrimination and noise-induced hearing loss is the main object of our study. Morphologic and enzyme-histochemical properties of the middle ear muscles of the rat indicate a complex, fine-tuned function of the middle ear muscles. Both middle ear muscles are merely composed of relatively small fast-twitch fibers. Almost all fibers possess an enzymatic profile that allows aerobic as well as anaerobic metabolism. The innervation of the muscles is extensive, and motor end plates are well developed. In a parallel study, middle ear muscle contraction (to be analyzed by electromyography) will be correlated with a change of the sound transmission characteristics of the middle ear (measured by the electrocochlear and brainstem auditory evoked responses). Preliminary results of the electrophysiologic measurements (electrocochleogram and brainstem auditory evoked response) are presented.     

Evaluation of brainstem function in patients with spasmodic dysphonia using vestibular evoked myogenic potentials and auditory brainstem responses

CONCLUSION: The vestibular area is closer than the auditory region to nucleus ambiguus. If a 'shared' lesion involves regions of adjacent nuclei of the brainstem in patients with spasmodic dysphonia then vestibular area involvement is more possible than that of the auditory region. OBJECTIVES: The authors hypothesize that lower brainstem lesions and involvement of descending pathways of the spinal tract may be the site of lesion in patients with spasmodic dysphonia. PATIENTS AND METHODS: Ten patients with spasmodic dysphonia were tested using the auditory brainstem response (ABR) and vestibular evoked myogenic potentials (VEMPs). RESULTS: No ABR abnormalities were found in right ears. Results of ABR on the left ear showed that one patient had abnormal ABR. This patient had severe sensorineural hearing loss on the left side. VEMPs displayed normal response in two patients bilaterally. First positive (p13) and second negative (n23) waves of VEMP could not be recorded in three cases unilaterally and in five patients bilaterally.     

The effect of noise exposure in the presence of canal fenestration on the amplitude of short-latency vestibular evoked potentials

BACKGROUND: Exposure to high-intensity noise causes little, if any, reduction in vestibular function in normal animals as shown by short-latency vestibular evoked potentials (VsEPs). OBJECTIVE: To investigate the effect of noise exposure on VsEPs following fenestration of the horizontal semicircular canal. DESIGN AND METHODS: Psammomys obesus (fat sand rat) underwent labyrinthectomy in 1 ear, while the lateral semicircular canal in the other ear was fenestrated. Control VsEPs to linear acceleration (approximately 3g; rise time, approximately 1-2 milliseconds) were recorded immediately after the operation. The experimental group animals were then subjected to loud white noise (113-dB sound pressure level) for 1 hour. Immediately after the noise exposure in the experimental group animals, VsEPs were once more recorded. RESULTS: The VsEPs in the experimental group animals were significantly reduced immediately following the noise exposure, while there was no change in the recordings from the control group animals (fenestrated but not noise exposed; noise exposed but not fenestrated), even though the noise exposure induced a mean 47-dB threshold elevation of the auditory brainstem response. CONCLUSIONS: The presence of the fenestration caused the vestibular end organs to become vulnerable to noise exposure. The fenestration may create a pathway enabling pressure release through the vestibular end organs during noise exposure, thus increasing the possibility of damage to the vestibular end organs. This did not occur in the intact, nonfenestrated animals.     

Evaluation of vestibular evoked myogenic potentials

In previous studies, electromyographic potentials, recorded in response to auditory clicks, have been attributed to stimulation of the otolith (saccule) and have been termed vestibular evoked myogenic potentials (VEMPs). In this study, we assessed the VEMPs in subjects with normal auditory brainstem evoked responses, with no history of vestibular symptoms or neck and other skeletal muscle abnormalities. To this effect, 32 subjects (64 ears), after ethics committee approval, were exposed to 75, 150, and 300 clicks at 100 dB, and the responses were averaged. Electromyographic activity was recorded by applying surface electrodes over the sternocleiodomastoid muscle under the following three conditions: no muscle contraction/no clicks, muscle contraction/no clicks, and muscle contraction/clicks. Our findings suggest that electromyographic responses have to be obtained, during muscle contraction, first without and then with clicks. Our data also suggest that comparison of these two recordings is necessary for meaningful results.     

术中经蜗窗龛电刺激记录听性脑干反应方法的建立及初步应用

目的 建立人工耳蜗手术中经蜗窗龛电刺激记录听性脑干反应的方法.方法 应用自制铂铱合金球形电极作为刺激电极,改装的人工耳蜗植入体连接体外言语处理器作为电刺激仪及Bio-logic Navigator Pro诱发电位仪,对17例不同病因(包括听神经病2例、耳蜗骨化1例、内耳畸形5例、脑白质异常1例,原因不明8例),不同年龄的人工耳蜗植入患者在手术中进行测试.植入人工耳蜗装置前,将刺激电极放置在蜗窗龛内,用电荷平衡双相脉冲电流经蜗窗龛进行电刺激,记录电诱发听性脑干反应.结果 17例患者均记录到明确的电诱发听性脑干反应波形,Ⅲ波和Ⅴ波的潜伏期分别为(2.12±0.18)ms 和(4.18±0.19)ms,阈值为(220.00±16.04)CL.其中2例听神经病、5例内耳畸形、1例耳蜗骨化、1例脑白质异常患者均记录到分化良好的波形.结论 电诱发听性脑干反应是一项能够较准确地反映听觉传导通路功能完整性的客观神经电生理测试方法,对于判断人工耳蜗植入后患者能否获得听性反应,具有重要的应用价值.本研究方法的安全性符合要求,听性反应的引出率高,值得推广应用.     

Usefulness of measuring electrically evoked auditory brainstem responses in children with inner ear malformations during cochlear implantation

Conclusions: EABR is a reliable and effective way of objectively confirming device function and implant-responsiveness of the peripheral auditory neurons up to the level of the brainstem in cases of inner ear malformation. Objective: To investigate the usefulness of measuring the intra-operative electrically evoked compound action potential (ECAP) and electrically evoked auditory brainstem response (EABR) in patients with and without congenital inner ear anomalies during cochlear implantation. Method: Thirty-eight consecutive children (40 ears) aged 5 or younger with congenital profound hearing loss. Twenty-four (25 ears) lacked congenital inner ear anomalies. The 14 patients (15 ears) with a malformation had common cavities (four ears), incomplete partition type I (three ears), cochlea hypoplasia type III (three ears), enlarged vestibular aqueduct (four ears), and cochlear nerve canal stenosis (one ear). Main outcome measures are ECAP and EABR responses. Results: Of the 25 ears lacking any malformation, 21, three, and one showed ‘Good’, ‘Variable’, and ‘No’ ECAP responses, respectively, and 24 and one showed ‘Good’ and ‘Variable’ intra-cochlear responses, respectively. Of the 15 ears with a malformation, two showed ‘Good’ ECAP responses, nine had ‘Variable’ ECAP responses, and four showed ‘No’ ECAP responses. Moreover, five showed ‘Good’ EABR responses and 10 showed ‘Variable’ EABR responses.     

Disappearance of click-evoked potentials on the neck of the guinea pig by pharmacological and surgical destruction of the peripheral vestibular afferent system

In order to establish an animal model of acoustically evoked vestibulo-collic reflex, the so-called vestibular evoked myogenic potential in humans, potentials evoked by loud clicks on the neck of the guinea pig were recorded using subjects whose peripheral vestibular endorgans or vestibular afferents had been damaged. Four normal control guinea pigs, four guinea pigs that received an intramuscular injection of gentamicin for 20 days (90 mg/kg/day) and five guinea pigs whose vestibular nerves were surgically sectioned were used in this study. Under general anesthesia with an intraperitoneal injection of pentobarbital sodium (40 mg/kg), auditory brainstem responses (ABRs) were recorded. Then, potentials evoked by loud clicks on the pre-vertebral muscle at the level of the third cervical vertebral bone were recorded using silver ball electrodes. As a result, a distinctive negative peak (NP) with a latency of 6-8 ms was recorded in all animals in the control group. NP was not observed in the gentamicin-administered group while ABR was preserved. After sectioning the vestibular nerve, NP was abolished while ABR was preserved. From these results, NP could be of vestibular origin. These results are in agreement with a previous report of NP using subjects whose cochlea had been damaged pharmacologically.     

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.