Cochlear hair cell damage from intermittent noise exposure in young and adult guinea pigs

A comparative study of age-dependent damage to cochlea from intermittent noise exposure was carried out on five-week-old and one-year-old pigmented guinea pigs. Hair cell loss in the organ of Corti was studied after five weeks' exposure to a pure tone stimulus (95 dB SPL at 2 kHz, one hour per day for five weeks). The noise-induced damage was sharply limited to the 7- and 11-mm marks from the apex. Damage was more marked in younger guinea pigs and was distinct from natural age-induced cell loss. When the 7- to 11-mm zone was further analyzed, outer hair cell damage appeared highly significant in both age groups but more severe in younger animals. Inner hair cell damage in this area was severe in both groups but statistically insignificant.     

Cochlear microcirculation in living guinea pigs following explosion

The cochlear microcirculation in living guinea pigs was observed, explosion was then imposed on the left ear and the velocity of blood cell flow and vessel diameters were measured within one hour. The results showed that: 1. there was an orderly stable movement of blood cells in all vascular beds under normal conditions; 2. the flow rate in both spiral ligament and stria vascularis increased promptly after explosion, that in the spiral ligament might return to normal within 30 minutes with vasodilatation, indicating increased blood supply early after explosion; 3. there was no relationship between changes in microcirculation and hearing loss and hair cell damage. The cause of hair cell damage and hearing loss were discussed and the techniques of vital microscopic studies of cochlear microcirculation assessed.     

Induced temporary threshold shift in guinea pigs

The etiology of an incidentally discovered temporary threshold shift observed in an experimental animal (Harley guinea pig) is discussed with its potential implications for auditory research.     

光化学法诱导豚鼠耳蜗微循环障碍模型

目的 通过光化学法建立豚鼠耳蜗微循环障碍模型以及观察血管纹、耳蜗毛细胞形态学变化.方法 ①将豚鼠随机分成5个组.实验组分成3个组,颈外静脉注入四氯四碘荧光素二钠(rose bengal,RB),用波长为(540±40)nm、光强为(500～600)mW/cm2绿光照射打开的听泡,各组选用不同光照时间诱导耳蜗微循环变化.对照组分2个组,对照Ⅰ组仅颈外静脉注入RB而不行光照;对照Ⅱ组不注入RB而仅行光照耳蜗.②分别对5个组动物行听性脑干反应及形态学检测.结果 ①每个实验组两次ABRⅢ波反应阈差异均有统计学意义(P＜0.05);②形态学观察实验组均出现耳蜗微循环障碍的变化,螺旋器以外毛细胞破坏为主.结论 采用光化学法可致耳蜗微循环障碍及毛细胞破坏,方法简便,易于实施,重复率高.     

Vestibular damage from chlorhexidine in guinea pigs

In the early 1970s the suspicion arose that chlorhexidine, a disinfectant extensively used for preoperative skin disinfection, was ototoxic if introduced into the middle ear cavity. It has previously been shown by the author that chlorhexidine causes damage to the organ of Corti of guinea pigs when introduced into the tympanic cavity. In the present study the toxic effect of chlorhexidine on the vestibular part of the inner ear is investigated. Middle ears of guinea pigs were exposed to chlorhexidine in two different concentrations in two different solvents. The duration of exposure was varied and the animals were sacrificed and examined at various periods.Damaged neuroepithelia were seen in most of the animals. The extent of damage was related to the concentration of chlorhexidine, to the duration of exposure and to the time lapse after exposure.     

Cochlear function of guinea pigs with experimental chronic renal failure.

This study aimed to evaluate electrophysiologically the cochlear function of guinea pigs that underwent a five-sixths nephrectomy and, additionally, to explore the synergistic action between chronic renal failure (CRF) and noise. Cochlear potentials were recorded at 1, 2, and 3 months postoperatively. Slight changes in compound action potential and cochlear microphonics were seen at 1 month postoperative, while moderate and profound changes were seen at 2 and 3 months. Endocochlear potential showed no significant reduction. The results indicate that CRF may be an etiologic factor for cochlear dysfunction and that the hair cells seem likely to be a main site of the lesion. One-month-postoperative animals were exposed to a broadband noise. In contrast to control animals, the test animals demonstrated no recovery from the decrease in compound action potential and cochlear microphonics that occurred immediately after noise exposure. This suggests a synergistic interaction between CRF and noise.     

紫杉醇对豚鼠听阈的影响

目的：探讨紫杉醇对豚鼠听阈的影响。方法：将30只雌性豚鼠随机分为6组（1个对照组和5个实验组,每组5只）,实验组分别予以不同剂量紫杉醇腹腔内注射,检测用药前、后各组动物ABR阈值。结果：实验组听力水平用药后均显著减低,相关分析显示,总药量与听力损失程度之间无显著相关性。结论：紫杉醇可导致轻到中度听力损失。     

Noise-induced inner ear damage in newborn and adult guinea pigs

Two-day (Group A), eight-day (Group B), and eight-month (Group C) old guinea pigs were exposed to 30 continuous hours of white noise at 119–120 db SPL. One month later pathology of the organ of Corti was evaluated and quantitated by use of the surface preparation technique. Percent cell damage was determined for outer hair, inner hair, outer pillar, and inner pillar cells at each of the four turns of the cochlea and for the cochlea as a whole. Comparisons of pathology of each cell type were made between groups. Mean percent outer hair cell damage per cochlea (± 1 S.E.) was 23.72 ± 3.69 for Group A, 36.98 ± 5.76 for Group B, and 7.24 ± 1.75 for Group C. There was no significant difference in outer hair cell damage between Groups A and B. Outer hair cells of Group A were significantly more damaged than those of Group C when damage in the cochlea as a whole was considered due to significantly greater damage in Group A at three and one half turns; likewise, outer hair cells of Group B were significantly more damaged than those of Group C when damage in the cochlea as a whole was considered due to significantly greater damage in Group B at two and one half and at three and one half turns. A similar effect was observed in terms of pathology of inner hair cells and pillar cells: there was a trend toward increased damage in animals of Groups A and B compared with C. Group C showed no outer or inner pillar cell damage, and only one of six animals had alterations in inner hair cells. In contrast, outer and inner pillar cells were damaged in Groups A and B, and four of six animals of Group A and six of eight of Group B showed inner hair cell damage. Recent electrophysiological and audiometric studies are discussed which, with the results of the present study, indicate greater susceptibility of young cochleas when compared with older cochleas, to noise-induced physiological and pathological alterations. It would seem medically prudent to take special precautions to avoid exposing newborns to excessive noise.     

Delayed-onset temporary auditory threshold shift following head blow in guinea pigs

This study attempts to investigate the development of sensorineural hearing loss following a head blow without skull fracture in association with physiological and histopathologic changes in an experimental animal model. With the head in a freely movable position, albino guinea pigs were given a single blow to the occipital region by a head blow device. At 1, 7, and 14 days after the blow, the animals' auditory brainstem response (ABR) and cochlear microphonics (CM) were examined, and both the temporal bone and brain stem were observed by light and electron microscopy. The ABR threshold was unchanged at day 1, was significantly increased at day 7, and was fully recovered at day 14. The I-V and I-II interpeak latencies were significantly prolonged at days 1 and 7, and wave I latency was significantly prolonged at day 7 only. These latencies were recovered to normal limits at day 14. On the other hand, no significant change in CM versus the control group was observed at any point in the measurements. Histopathologically, no abnormal finding was seen at the light microscopic level. However, at the electron microscopic level, there were some injuries to the eighth nerve. At day 1, the lamellar structure of the myelin sheath was irregular, and the periaxonal space was expanded; at day 7, the myelin sheath was disintegrated. At day 14, however, these changes were partially reversed. These results suggest that sensorineural hearing loss following a head blow in this model is attributed to dysfunction of the eighth nerve rather than to cochlear impairment.     

Inhibition of caspases alleviates gentamicin-induced cochlear damage in guinea pigs

The efficacy of caspase inhibitors for protecting the cochlea was evaluated in an in vivo study using guinea pigs, as the animal model system. Gentamicin (12 mg/ml) was delivered via an osmotic pump into the cochlear perilymphatic space of guinea pigs at 0.5 microl/h for 14 days. Additional animals were given either z-Val-Ala-Asp (Ome)-fluoromethyl ketone (z-VAD-FMK) or z-Leu-Glu-His-Asp-FMK (z-LEHD-FMK), a general caspase inhibitor and a caspase 9 inhibitor, respectively, in addition to gentamicin. The elevation in auditory brain stem response thresholds, at 4, 7, and 14 days following gentamicin administration, were decreased in animals that received both z-VAD-FMK and z-LEHD-FMK. Cochlear sensory hair cells survived in greater numbers in animals that received caspase inhibitors in addition to gentamicin, whereas sensory hair cells in animals that received gentamicin only were severely damaged. These results suggest that auditory cell death induced by gentamicin is closely related to the activation of caspases in vivo.     

Involvement of nitric oxide generation in noise-induced temporary threshold shift in guinea pigs

The present study explored the role of endogenous nitric oxide (NO) in the temporary threshold shift caused by acoustic trauma. Guinea pigs were exposed to broadband white noise at a level of 105+/-2dB sound pressure level (SPL) for 10min, causing a temporary threshold shift (TTS). The guinea pigs were divided into six groups (N-1 to N-6) according to survival days after noise exposure (0, 1, 2, 3, 7, 28days). Auditory brainstem responses (ABR) were recorded before noise exposure, immediately after noise exposure and before sacrifice. Immediately after animals were sacrificed, the stria vascularis and the spiral ligament of the lateral wall of each individual cochlea were harvest as a unit and prepared for assay of NO. There was a significant correlation (P<0.001) between the NO concentration and final ABR threshold in the noise exposure groups. But the return of ABR threshold to pre-noise-exposed level is early than that of NO concentration. An average 16.2dB threshold shift was found immediately after noise exposure. The threshold returned to the pre-noise-exposed level on the second post-exposure day. Comparing to unexposed control animals, the NO concentration increased nearly threefold immediately following noise exposure and decreased to twofold when the hearing threshold had returned to the pre-noise-exposed level. On the seventh post-exposure day the NO concentration was not different from that in unexposed control animals. Those findings indicate that endogenous NO is generated in the noise-induced temporal threshold shift and its concentration is correlated with the hearing loss.     

腺病毒携带EGFP基因经完整圆窗膜转导豚鼠耳蜗的实验研究

目的研究腺病毒携带目的基因经完整圆窗膜途径耳蜗转导的可行性及安全性，为内耳基因治疗提供实验基础和理论依据。方法20只白色红目豚鼠，术前及术后分别行听性脑干反应（ABR）检查。实验组（12只）以重组腺病毒携带的增强型绿色荧光蛋白基因（enhancedgreenfluorescentprotein，EGFP），对照组（8只）以人工外淋巴液注入豚鼠圆窗龛内。分别于术后5天、14天取双侧耳蜗标本做基底膜铺片，耳蜗冰冻切片观察。结果于圆窗龛内注入腺病毒携带目的基因的转导方法对听力无明显影响。转染耳蜗及对侧耳蜗内目的基因呈广泛表达。5天组表达产物最高，14天组逐渐降低。对照组耳蜗未见EPFP表达。结论于圆窗龛内注入腺病毒携带目的基因转导的方法对耳蜗无明显毒害作用，且能够将目的基因成功转导至双侧耳蜗组织并广泛表达。     

Bilateral superior cervical sympathectomy and noise-induced, permanent threshold shift in guinea pigs.

The rich sympathetic innervation to the cochlea suggests its potential control of cochlear blood flow and activity during noise exposure, as part of the general and local stress sympathetic reaction evoked by noise. In a previous study, superior cervical sympathectomy prior to sound exposure in guinea pigs in an awake state, resulted in reduced temporary threshold shift. The present study was conducted to explore whether this potential protection would also be manifested in conditions producing permanent threshold shift (PTS). Thirty-six guinea pigs, divided into four groups of nine guinea pigs each, were sound exposed for 2 h in an awake state. Eighteen guinea pigs underwent superior cervical sympathectomy prior to sound exposure. Auditory brainstem thresholds were recorded prior to sound exposure, and then at 24 h, 1 and 6 weeks post-exposure. Results indicated a reduced PTS at 122 dB sound pressure level (SPL) exposure, suggesting a protective effect of the sympathectomy. However, at 125 dB SPL exposure, the protective effect was reduced.     

Auditory function in guinea pigs treated with netilmicin and other aminoglycoside antibiotics

Summary The following aminoglycoside antibiotics netilmicin, sisomicin, gentamicin, and kanamycin were submitted to a comparative study of their ototoxicity using both reflexological (Preyer's pinnareflex) and electrophysiological (near and far field) methods. The daily s.c. administration of sisomicin, gentamicin, and kanamycin for 21 days provoked a dose-related impairment of the cochlear function, detected with all the employed techniques. On the other hand, a very low ototoxic effect of netilmicin was demonstrated with electrophysiological but not with the reflexological evaluation.The reliability of the methods used in these experiments is also compared.     

Nitric oxide synthase inhibitor reduces noise-induced cochlear damage in guinea pigs

Conclusion. The results obtained in this study indicate that N^G-nitro-L-arginine methyl ester (L-NAME) protects cochlear damage from acoustic trauma through reducing the production of nitric oxide (NO). Objectives. This study aimed to explore whether NO synthase inhibitor L-NAME could reduce cochlear damage in acoustic trauma. Materials and methods. Seventy guinea pigs (300–350g) were divided randomly into four groups (n=20 in groups I, III, and IV; n=10 in group II). Two days consecutively and 30min before noise exposure (4kHz octave band, 115dB SPL 5h), subjects received an injection of 5ml saline/kg (groups I and III) or 10mg/kg L-NAME (groups II and IV). Sham-exposed guinea pigs were listed as groups I and II. Protection was assessed physiologically by the change in auditory brainstem response (ABR) threshold and histologically by survival of outer hair cells (OHCs). NO level of cochlear tissue was assayed 3days after noise exposure. Results. Group III showed significantly greater OHC loss, threshold shifts and NO level compared with group I and group IV. Compared with group III, noise-induced elevation in NO level in the cochlea was significantly attenuated by L-NAME (p<0.001).     

Nitric oxide synthase inhibitor reduces noise-induced cochlear damage in guinea pigs

CONCLUSION: The results obtained in this study indicate that NG-nitro-L-arginine methyl ester (L-NAME) protects cochlear damage from acoustic trauma through reducing the production of nitric oxide (NO). OBJECTIVES: This study aimed to explore whether NO synthase inhibitor L-NAME could reduce cochlear damage in acoustic trauma. MATERIALS AND METHODS: Seventy guinea pigs (300-350g) were divided randomly into four groups (n=20 in groups I, III, and IV; n=10 in group II). Two days consecutively and 30min before noise exposure (4kHz octave band, 115dB SPL 5h), subjects received an injection of 5ml saline/kg (groups I and III) or 10mg/kg L-NAME (groups II and IV). Sham-exposed guinea pigs were listed as groups I and II. Protection was assessed physiologically by the change in auditory brainstem response (ABR) threshold and histologically by survival of outer hair cells (OHCs). NO level of cochlear tissue was assayed 3days after noise exposure. RESULTS: Group III showed significantly greater OHC loss, threshold shifts and NO level compared with group I and group IV. Compared with group III, noise-induced elevation in NO level in the cochlea was significantly attenuated by L-NAME (p<0.001).