听神经病实验动物模型

听神经病的临床听力学特征主要表现在具有正常的耳蜗感受器电位和异常的听性脑干反应波形以及对语言的理解障碍,其病理学改变部位被确定是在周边听觉系统,主要表现在内毛细胞缺损、听神经末梢破坏、听神经纤维脱髓鞘病变、螺旋神经节细胞缺损,或上述一个或几个部位同时发生病变。本文介绍了模拟听神经病的各种实验动物模型,其中包括模拟单纯内毛细胞缺损的Slc19a2基因缺陷小鼠和Ggt1基因缺陷小鼠实验模型;模拟单纯Ⅰ型传入神经末梢损害的谷氨酸盐实验模型;模拟单纯脱髓鞘病变的甘油实验模型;模拟Ⅰ型螺旋神经节及其神经纤维损害的乌苯酐实验模型和免疫性疾病损害模型;模拟单纯神经纤维脱髓鞘病变的胆红素实验模型和髓鞘缺陷仓鼠模型;模拟单纯听神经近端脱髓鞘病变的阿霉素模型和压力夹伤听神经实验模型;以及模拟整个周边听觉系统全程病变的卡铂南美栗鼠实验模型。这些实验模型可以分别用于模拟听神经病的一种或几种临床表现及病变特征的实验研究。     

激光耳显微外科动物模型的建立

目的重点探讨激光耳显微外科动物模型建立过程中如何选择最佳的麻醉方式、手术入路及激光种类。方法选用健康雄性听力正常的豚鼠70只,随机分为A组、B组及C组,其中A、B组各20只,C组30只,分别以速眠新、氯胺酮及复合麻醉,比较三组动物的存活率,并随机观察每组10只豚鼠麻醉后的苏醒时间,然后选用平对外耳道口的耳后入路打开听泡后壁暴露耳蜗底周和圆窗龛,采用CO2激光进行耳蜗底周造孔。结果 C组(复合麻醉组)动物存活率最高(p相似文献   

Effect of Rutin on Diabetic Auditory Neuropathy in an Experimental Rat Model

ObjectivesDiabetic auditory neuropathy is a common complication of diabetes mellitus that has a major impact on patients’ quality of life. In this study, we assessed the efficacy of rutin in treating diabetic auditory neuropathy in an experimental rat model.MethodsForty Sprague-Dawley rats were randomly assigned to the following groups: group 1, control; group 2, diabetic rats; and groups 3–5, rats treated with rutin (at doses of 50, 100, and 150 mg/kg, respectively). We used auditory brain stem response, stereology of the spiral ganglion, and measurements of superoxide dismutase (SOD) and malondialdehyde (MDA) to evaluate the effects of treatment.ResultsSignificant improvements in auditory neuropathy were observed in the rutin-treated groups in comparison with the diabetic group (P<0.05). Auditory threshold, wave latency, wave morphology, the volume and number of neurons in the spiral ganglion, and SOD and MDA activity showed improvements following treatment.ConclusionRutin shows promise as a treatment modality for diabetic auditory neuropathy, but more trials are warranted for its clinical application.     

Temporal Pitch Sensitivity in an Animal Model: Psychophysics and Scalp Recordings

Journal of the Association for Research in Otolaryngology - Cochlear implant (CI) users show limited sensitivity to the temporal pitch conveyed by electric stimulation, contributing to impaired...     

Bilateral Dorsal Cochlear Nucleus Lesions Prevent Acoustic-Trauma Induced Tinnitus in an Animal Model

Animal experiments suggest that chronic tinnitus (“ringing in the ears”) may result from processes that overcompensate for lost afferent input. Abnormally elevated spontaneous neural activity has been found in the dorsal cochlear nucleus (DCN) of animals with psychophysical evidence of tinnitus. However, it has also been reported that DCN ablation fails to reduce established tinnitus. Since other auditory areas have been implicated in tinnitus, the role of the DCN is unresolved. The apparently conflicting electrophysiological and lesion data can be reconciled if the DCN serves as a necessary trigger zone rather than a chronic generator of tinnitus. The present experiment used lesion procedures identical to those that failed to decrease pre-existing tinnitus. The exception was that lesions were done prior to tinnitus induction. Young adult rats were trained and tested using a psychophysical procedure shown to detect tinnitus. Tinnitus was induced by a single unilateral high-level noise exposure. Consistent with the trigger hypothesis, bilateral dorsal DCN lesions made before high-level noise exposure prevented the development of tinnitus. A protective effect stemming from disruption of the afferent pathway could not explain the outcome because unilateral lesions ipsilateral to the noise exposure did not prevent tinnitus and unilateral lesions contralateral to the noise exposure actually exacerbated the tinnitus. The DCN trigger mechanism may involve plastic circuits that, through loss of inhibition, or upregulation of excitation, increase spontaneous neural output to rostral areas such as the inferior colliculus. The increased drive could produce persistent pathological changes in the rostral areas, such as high-frequency bursting and decreased interspike variance, that comprise the chronic tinnitus signal.     

Diagnosis of Head and Neck Precancerous Lesions in an Animal Model Using Fluorescence Spectroscopy

Laser-induced fluorescence (LIF) of tissues depends on their biochemical and histomorphologic characteristics. LIF spectroscopic properties of 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced precancerous and early cancerous lesions in a hamster buccal pouch mucosa model were studied. Fluorescence spectra from neoplastic lesions showed a characteristic fluorescence peak in the red region of the visible spectrum centered between 630 and 640 nm when excited with 410-nm light. Using this as a diagnostic criterion, 45 of 49 lesions studied were correctly diagnosed, including early dysplastic lesions. Follow-up study of four dysplastic lesions over 2 weeks revealed an increase in red fluorescence intensity. The findings of these experiments suggest that LIF spectroscopy may be a valuable noninvasive technique not only for early diagnosis of head and neck cancer, but also to probe a possible biochemical surrogate biomarker in the follow-up of suspected lesions.     

Thermal Effects of Laser Stapedectomy in an Animal Model: CO2 Versus KTP

Although use of the laser for stapedectomy has become common in recent years, controversy remains regarding whether the CO₂ or visible-spectrum lasers (argon and KTP) are best suited for this operation. The main concern has been the potential for thermal injury to the inner ear with the visiblespectrum lasers attributable to their absorption characteristics. To further investigate this issue, the author performed 20 laser stapedectomies on adult chinchillas. Following placement of a 0.127-mm-diameter copper/constantan thermocouple (sampling at 12 Hz) beneath the footplate on the medial wall of the vestibule via a distant fenestration site, thermal changes with a micromanipulator-based CO₂ and fiberoptic KTP system were compared. This was the first live animal model comparison of these two lasers. There was no statistical difference in the mean temperature elevation between the two systems ( P = 0.395).     

Sensorineural Hearing Loss after Vibration: an Animal Model for Evaluating Prevention and Treatment of Inner Ear Hearing Loss

Sensorineural hearing loss following a variety of acoustic trauma, including middle ear surgery, is well known. Current literature, which points to the deleterious influence of noise on the inner ear during surgery, has yet to assess the influence of vibration generated by the burr. The purpose of the study reported here was to establish an animal model that mimics drilling and can be used to explore methods of hearing loss prevention and treatment. A specially developed electromagnetic vibrator was calibrated and used in 59 guinea pigs to induce hearing loss. Both young and old guinea pigs were used. The bony external ear canal of guinea pigs were exposed to vibration or sound of varying duration and intensity. The vibration of the temporal bone and noise level in the middle ear were measured. Electrocochleography was recorded to evaluate the hearing loss. Among the young animals, 90% developed a significant threshold shift (TS &gt;20 dB), when vibrated with 250 Hz at an intensity of 6.2 m/s² for 15 min. An average of 42 dB TS was observed. With 10 min exposure 63% showed a TS. The older animals vibrated for 5 min developed the same TS (mean TS 34 dB) as the young animals when vibrated for 10 min. The vibration-induced TS showed no recovery within 3 days of observation. In the contralateral ear 4 out of 5 animals showed TS&gt;20 dB. When exposed to sound levels exceeding the vibration-generated sound in the middle ear (119 dB at 250 Hz) only 2 out of 11 animals (18%) showed TS. The frequency of TS and level of TS were significantly greater in the vibrated animals than in sound-only exposed animals (p&lt;0.01). The degree of vibration-induced TS in the present animal model could be controlled by vibration intensity and duration. The older animals were more susceptible to vibration-induced inner-ear damage than younger animals. This model will be used in further studies to find methods for prevention and treatment of hearing loss during ear surgery.     

Vigabatrin,a GABA Transaminase Inhibitor,Reversibly Eliminates Tinnitus in an Animal Model

Animal models have facilitated basic neuroscience research investigating the pathophysiology of tinnitus. It has been hypothesized that partial deafferentation produces a loss of tonic inhibition in the auditory system that may lead to inappropriate neuroplastic changes eventually expressed as tinnitus. The pathological down-regulation of γ-amino butyric acid (GABA) provides a potential mechanism for this loss of inhibition. Using an animal model previously demonstrated to be sensitive to treatments that either induce or attenuate tinnitus, the present study examined the effect of the specific GABA agonist vigabatrin on chronic tinnitus. It was hypothesized that vigabatrin would decrease the evidence of tinnitus by restoring central inhibitory function through increased GABA availability. Vigabatrin has been demonstrated to elevate central GABA levels (Mattson et al. 1995). Tinnitus was induced in rats using a single 1-h unilateral exposure to band-limited noise, which preserved normal hearing in one ear. Psychophysical evidence of tinnitus was obtained using a free-operant conditioned-suppression method: Rats lever-pressed for food pellets and were trained to discriminate between the presence and absence of sound by punishing lever pressing with a mild foot shock (0.5 mA; 1 s) at the conclusion of randomly introduced silent periods (60 s) inserted into background low-level noise. Additional random insertion of pure tone and noise periods of variable intensity enabled the derivation of psychophysical functions that reflected the presence of tinnitus with features similar to 20-kHz tones. Vigabatrin was chronically administered via drinking water at 30 and 81 mg kg⁻¹ day⁻¹, with each dose level tested over 2 weeks, followed by a 0-mg washout test. Vigabatrin completely and reversibly eliminated the psychophysical evidence of tinnitus at both doses. Although vigabatrin has serious negative side effects that have prevented its clinical use in the USA, it is nevertheless a potentially useful tool in unraveling tinnitus pathophysiology.     

Establishing functional language in an autistic child: A cooperative approach

The case study of a 7-yr-old boy who was diagnosed as autistic is reported. The cooperative efforts of a teacher of the severely emotionally disturbed, a speech pathologist, and the child's parents were combined to create an optimal situation for the facilitation of behavior change and language development. Examples of the procedures used and the child's progress over a 2$\text{1}\text{2}$-yr period are presented and described.     

光化学法建立豚鼠耳蜗微循环障碍模型的初步报告

为建立较好的耳蝇微循环障碍模型，采用豚鼠股静脉内注射四碘四氯荧光素二钠，以波长为５５０±２０ｎｍ绿色光束照射耳蜗的方法，诱导豚鼠耳蜗血管内发生光化学反应，损伤血管内皮细胞，血小板被受损的内皮细胞激活，粘附、聚集于内皮细胞表面或暴露的基膜上形成微血栓，导致耳蜗微循环障碍，耳蜗血流量（ＣＢＦ）骤降，复合动作电位（ＣＡＰ）振幅下降乃至消失。随着时间的延长，耳蜗血管纹、Ｃｏｒｔｉ器、螺旋神经节细胞等结构先后出现不同程度的缺血性病变，与某些病理条件下的耳蜗微循环障碍有很大的相似性。这种方法，可以为研究内耳微循环障碍或缺血性损伤机制，以及筛选治疗药物建立较为理想的动物模型。     

耳鸣动物行为学模型的制作

目的 改进饮水抑制法耳鸣动物模型，为耳鸣研究提供一种更为实用的动物模型。方法 健康Wistar大鼠18只，随机平均分成3组，第1、2组为水杨酸钠组，腹腔注射水杨酸钠，每日350mg／k异，第3组为生理盐水组，腹腔注射等量生理盐水。给药时间为训练前3小时，其中，第1、3组动物在条件反射建立前即开始给药，第2组动物在条件反射消退期开始给药。适应性喂养1周后禁水2天，将干渴的动物置于隔声室内进行条件反射训练，训练只在夜晚进行，隔声室内持续给予背景白噪声，强度为72dB SPL，以背景噪声停止为条件刺激，电击为非条件刺激，将条件刺激出现前后各1min动物的舔水时间作为观察指标。经强化训练后形成“背景噪声停止-舔水减少”的条件反射。最后，所有动物不再给予电击，观察条件反射的消退时间，以判断动物是否产生耳鸣。结果 经过3～5天的条件反射训练，所有动物均建立了稳定的条件反射。在消退期，第1组动物条件反射的消退时间最长，第2组最短，第3组居中，统计分析显示，各组间的差别均具有显著统计学意义，说明大鼠注射水杨酸钠后确实产生了耳鸣。结论 在饮水抑制法耳鸣动物模型的制作过程中，用“舔水时间”代替“舔水率”同样能够证实水杨酸钠造成动物耳鸣，且所需设备简单，方法切实可行。     

耳鸣动物行为学模型的制作

目的 建立食物抑制法耳鸣动物模型，为耳鸣研究提供一种客观手段。方法 雄性健康wistar大鼠30只，随机平均分成6组。第1、2组为水杨酸钠组，皮下注射水杨酸钠(salicylic acid缩写为SA)，每日350mg/kg体重；第3、4组为生理盐水组；第5、6组为尼莫地平组，注射水杨酸钠后再皮下注射尼莫地平每日1mg儿g体重。在隔声室一周的适应期内，只在夜间给动物投放食物，进入实验期开始禁食。将禁食后非常饥饿的动物置于另-隔声室内进行条件反射训练。训练只在夜晚进行。实验期间动物所处的两个隔声室持续给予背景白噪声，强度为55dB(SPL)。第l、3、5组从条件反射建立前开始给药。训练时给动物供食并记录摄食次数。背景噪声停止为条件刺激，电击为非条件刺激。经强化训练后形成“背景噪声停止—摄食减少或停止”的条件反射。第2、4、6组在条件反射建立后开始给药。最后，所有动物不再给予电击，观察条件反射的消退期时间，以判断动物是否产生耳鸣。结果 各组动物的消退时间经方差分析显示具有显著性意义。说明大鼠注射水杨酸钠后有耳鸣产生，尼莫地平能够消除水杨酸钠诱发的耳鸣。动物夜间训练兴奋性良好，造模成功率达到96．7％。结论 食物抑制法耳鸣动物模型证实水杨酸钠造成动物产生耳鸣的存在。本实验方法切实可行，可重复性良好。     

Neural ITD Sensitivity and Temporal Coding with Cochlear Implants in an Animal Model of Early-Onset Deafness

Journal of the Association for Research in Otolaryngology - Users of cochlear implant (CI) face challenges in everyday situations such as understanding conversations in noise, even with CIs in both...     

慢性鼓膜穿孔动物模型的构建

目的建立慢性鼓膜穿孔的动物模型。方法将10只豚鼠于麻醉后在显微镜下以虹膜切开刀将豚鼠鼓膜双侧紧张部前方部分切除，以耳显微刮匙刮除鼓膜穿孔边缘鼓室侧黏膜上皮，于穿孔四角放射性切开1mm后将创缘内翻。术后每日于麻醉后在显微镜下观察鼓膜愈合情况。8周后于光镜下观察穿孔鼓膜结构。结果10只豚鼠共加耳鼓膜中16耳鼓膜经2个月未能愈合(80％)。所有穿孔均占紧张部面积约40％左右。3耳鼓膜感染。1耳鼓膜经10次手术后仍自行愈合。结论通过鼓膜部分切除加边缘内翻的方法可以成功地建立慢性鼓膜穿孔的动物模型。     

Early Sensorineural Hearing Loss in Ob/Ob Mouse, an Animal Model of Type 2 Diabetes

Objectives

There have been many studies on the relationship between diabetes mellitus and presbycusis. Microangiopathy and neuropathy that''s caused by chronic hyperglycemia may lead to damage to the inner ear. Several clinical studies on humans and animal studies have been performed to investigate the association between diabetes and hearing loss, however, this relationship is still a matter of debate. We investigated the association of diabetes and sensorineural hearing loss in an animal model of type-2 diabetes and obesity (the ob/ob mouse [OM]).

Methods

The auditory brainstem response (ABR) thresholds were obtained in the OM and the wild type mice (C57BL/6J mice) up to 25 weeks after birth. After the animals were sacrificed, their cochleae were retrieved and then subjected to histopathologic observations.

Results

The OM exhibited significantly elevated ABR thresholds at 21 weeks of age, yet the C57BL/6J mice exhibited no significant change until 25 weeks of age. On the histological findings, outer hair cell degeneration and loss of spiral ganglion cells were observed in the middle and basal turns of the OM. On the contrary, no degenerative change was observed until 25 weeks of age in the C57BL/6J mice.

Conclusion

This study suggests that chronic hyperglycemia and obesity may lead to early sensorineural hearing loss.     

Chronic Reduction of Endocochlear Potential Reduces Auditory Nerve Activity: Further Confirmation of an Animal Model of Metabolic Presbyacusis

Gerbils aged in quiet show a decline of the endocochlear potential (EP) and elevated auditory nerve compound action potential (CAP) thresholds. However, establishing a direct relationship between an age-related reduction in the EP and changes in the activities of primary auditory neurons is difficult owing to the complexity of age-related histological changes in the cochlea. To address this issue, we developed a young gerbil model of “metabolic” presbyacusis that uses an osmotic pump to deliver furosemide into the round window niche for 7 days, resulting in a chronically reduced EP. In this model, the only major histopathologic changes were restricted to the hook region of the cochlea and consisted of loss of strial intermediate cells and massive edema in the lateral wall. The morphological and physiological evidence suggests that the cochlea can adapt to furosemide application over time. The morphology of spiral ganglion cells and hair cells appeared normal throughout the cochlea. CAP responses and EP values in this model are similar to those of quiet-aged ears. The spontaneous activity of single auditory fibers (n = 188) was assessed in 15 young gerbils treated with furosemide for 7 days. The percentage of recorded low-spontaneous rate (SR) fibers at characteristic frequencies (CFs) ≥ 6 kHz was significantly lower in furosemide-treated than in control ears. Recovery function tests of CAP responses after prior stimulation also showed a decline in activity of the low-SR population with CFs ≥ 6 kHz in the treated cochleas. A similar loss in the activity of low-SR fiber has been previously shown in quiet-aged gerbils. These results suggest that dysfunction of the cochlear lateral wall and subsequent chronic reduction in the EP can directly affect the activity patterns of primary auditory neurons in a manner similar to that seen in aged gerbils.     

伴周围神经病变听神经病患者的临床特征分析

目的分析一组伴周围神经病变听神经病患者的临床症状特点和听力学特征,总结综合征型听神经病的遗传学和表型特征。方法对课题组2003年至2018年间收集的听神经病患者采用统一问卷调查,记录发病年龄和临床症状特点,并进行标准化的听力学评估:包括纯音测听、听性脑干反应(ABR)、声导抗、畸变产物耳声发射(DPOAE)、耳蜗电图(ECochG)、言语识别率测试。结果 2003-2018年共收集听神经病患者531例,伴周围神经病变者69例,占12.99%;其中男性32例,女性37例,男女比例为1:1.16;发病年龄在0-26岁,平均14.85±5.23岁,其中婴幼儿期(≤3岁)发病4例,占5.79%;儿童期(3-12岁)发病10例,占14.49%;青少年期(12-18岁)发病36例,占52.17%;成人(≥18岁)发病19例,占27.54%。44例(63.77%)患者首发为听神经病,另25例(36.23%)首发为视力下降、四肢麻木、走路不稳等周围神经病变的表现;54例(78.26%)伴有耳鸣,7例(10.14%)伴有眩晕或前庭功能障碍。纯音听力图以低频上升型听力曲线为主,占66.92%;听力损失程度主要表现为轻、中度听力损失,占68.46%。结论听神经病可伴发多种神经系统疾病,多表现为周围神经病变,如四肢麻木、肌张力低下、共济失调、视力下降等。综合征型听神经病患者的首发症状可以是听神经病,也可以是其他神经系统疾病,其听力学评估结果符合听神经病的听力学特征。