Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome.

Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7(Gt)(/+) mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7(Gt)(/+) mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7(Gt)(/+) mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7(Gt)(/+) mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears.

Biosilicate ototoxicity and vestibulotoxicity evaluation in guinea-pigs.

UNLABELLED: Changes, destructions and interruptions in middle ear ossicular chain architecture may be caused by infection, trauma, tumors, congenital alterations or prior surgeries. Nonetheless, infectious and inflammatory processes, focal or generalized which affect the middle ear are the most prevalent, causing a great demand for ossiculoplasty. Biosilicato is a new material which can be used in the middle ear with the goal of reconstructing the ossicular chain. It is a bioactive type A vitroceramic, in other words, it binds to bone or soft tissue in a matter of a few hours, thanks to the formation of hydroxy-carbonateapatatie in its contact surface when in contact with body fluids. AIMS: The goal of the present paper is to assess biosilicate ototoxicity and vestibular toxicity in experimental animals, for later use in humans. MATERIALS AND METHODS: This a clinical and experimental study in which otoacoustic emissions were performed before and after the placement of Biosilicate in the middle ear of experimental animals and a scanning electron microscopy was carried out in the cochlea, saccule, utriculus and macula of the semicircular canals after 30 and 90 days to assess oto and vestibular toxicity. RESULTS: There were no signs of oto or vestibular toxicity in any of the groups associated with biosilicate. CONCLUSION: Biosilicate is a safe material to be used in ossiculoplasties.

Biosilicate® Ototoxicity and Vestibulotoxicity evaluation in guinea-pigs / Avaliação da ototoxicidade e vestibulotoxicidade do biosilicato® em orelhas de cobaias

Changes, destructions and interruptions in middle ear ossicular chain architecture may be caused by infection, trauma, tumors, congenital alterations or prior surgeries. Nonetheless, infectious and inflammatory processes, focal or generalized which affect the middle ear are the most prevalent, causing a great demand for ossiculoplasty. Biosilicato® is a new material which can be used in the middle ear with the goal of reconstructing the ossicular chain. It is a bioactive type A vitroceramic, in other words, it binds to bone or soft tissue in a matter of a few hours, thanks to the formation of hydroxy-carbonateapatatie in its contact surface when in contact with body fluids. AIMS: The goal of the present paper is to assess biosilicate ototoxicity and vestibular toxicity in experimental animals, for later use in humans. MATERIALS AND METHODS: This a clinical and experimental study in which otoacoustic emissions were performed before and after the placement of Biosilicate in the middle ear of experimental animals and a scanning electron microscopy was carried out in the cochlea, saccule, utriculus and macula of the semicircular canals after 30 and 90 days to assess oto and vestibular toxicity. RESULTS: There were no signs of oto or vestibular toxicity in any of the groups associated with biosilicate. CONCLUSION: Biosilicate is a safe material to be used in ossiculoplasties

As alterações, destruições e interrupções da arquitetura da cadeia ossicular da orelha média podem ser causadas por infecções, trauma, tumores, alterações congênitas ou cirurgias prévias. Entretanto os processos inflamatórios e infecciosos, focais ou generalizados que acometem a orelha média são os mais prevalentes, gerando uma enorme demanda de ossiculoplastias. O Biosilicato® é um novo material que pode ser usado em orelhas médias com o objetivo de reconstruir a cadeia ossicular. Constitui-se de uma vitrocerâmica bioativa do tipo A, ou seja, que se liga a tecido ósseo ou a tecido mole em algumas horas, devido à formação de hidroxicarbonatoapatita em sua superfície de contato quando em contato com fluidos corpóreos. OBJETIVO: O objetivo deste trabalho é avaliar a ototoxicidade e vestibulotoxicidade do Biosilicato em cobaias, para posterior utilização em humanos. MATERIAL E MÉTODO: Trata-se de um estudo clínico e experimental, onde foram realizadas emissões otoacústicas antes e após a colocação de Biosilicato na orelha média de cobaias e realizada microscopia eletrônica de varredura da cóclea, sáculo, utrículo e máculas dos canais semicirculares após 30 e 90 dias para avaliar a oto e vestibulotoxicidade. RESULTADOS: Não houve sinais de oto ou vestibulotoxicidade em nenhum dos grupos relacionados ao Biosilicato. CONCLUSÃO: O Biosilicato é um material seguro para ser usado em ossiculoplastias.

The effects of high-intensity, low-frequency active sonar on rainbow trout.

This study investigated the effects on rainbow trout (Oncorhynchus mykiss) of exposure to high-intensity, low-frequency sonar using an element of the standard Surveillance Towed Array Sensor System Low Frequency Active (LFA) sonar source array. Effects of the LFA sonar on hearing were tested using auditory brainstem responses. Effects were also examined on inner ear morphology using scanning electron microscopy and on nonauditory tissues using general pathology and histopathology. Animals were exposed to a maximum received rms sound pressure level of 193 dB re 1 microPa(2) for 324 or 648 s, an exposure that is far in excess of any exposure a fish would normally encounter in the wild. The most significant effect was a 20-dB auditory threshold shift at 400 Hz. However, the results varied with different groups of trout, suggesting developmental and/or genetic impacts on how sound exposure affects hearing. There was no fish mortality during or after exposure. Sensory tissue of the inner ears did not show morphological damage even several days post-sound exposure. Similarly, gross- and histopathology observations demonstrated no effects on nonauditory tissues.

The inner ear morphology and hearing abilities of the Paddlefish (Polyodon spathula) and the Lake Sturgeon (Acipenser fulvescens).

Concern regarding the spread of silver carp (Hypopthalmichthys molitrix) and bighead carp (Aristichthysc nobilis) through the Illinois River has prompted the development of an Acoustic Fish Deterrent (AFD) system. The application of this technology has resulted in a need to understand the auditory physiology of fish other than the target species, in order to minimise the effect of the AFD barrier on the ecology of indigenous fish populations. To this end, both the structures involved in sound reception and the hearing abilities of the paddlefish (Polyodon spathula) and the lake sturgeon (Acipenser fulvescens) are studied here using a combination of morphological and physiological approaches, revealing that both fish are responsive to sounds ranging in frequency from 100 to 500 Hz. The lowest hearing thresholds from both species were acquired from frequencies in a bandwidth of between 200 and 300 Hz, with higher thresholds at 100 and 500 Hz. The rationale for studying hearing in P. spathula and A. fulvescens in particular, is the value placed on them by both the commercial caviar producing industry and by the recreational fisheries sector. The hearing abilities of twelve P. spathula and twelve A. fulvescens were tested in sound fields dominated by either sound pressure or particle motion, with the results showing that acipenseriform fish are responsive to the motion of water particles in a sound field, rather than the sound pressure component. In this study, we measure the intensity of the sound field required to evoke threshold responses using a pressure sensitive hydrophone, as pressure dominated sound fields are the most audible acoustic condition for specialists like H. molitrix and A. nobilis (the target species). The results of the auditory examination clearly show that P. spathula and A. fulvescens are not sensitive to sound pressure, and will therefore have a significantly higher deterrent threshold than H. molitrix and A. nobilis in a pressure dominated sound field.

Functional morphology of the inner ear and underwater audiograms of Proteus anguinus (Amphibia, Urodela).

Octavolateral sensory organs (auditory and lateral line organs) of cave salamander Proteus anguinus are highly differentiated. In the saccular macula of the inner ear the complex pattern of hair cell orientation and the large otoconial mass enable particle displacement direction detection. Additionally, the same organ, through air cavities within the body, enables detection of underwater sound pressure changes thus acting as a hearing organ. The cavities in the lungs and mouth of Proteus are a resonators that transmit underwater sound pressure to the inner ear. Behaviourally determined audiograms indicate hearing sensitivity of 60 dB (rel. 1 microPa) at frequencies between 1 and 10 kHz. The hearing frequency range was between 10 Hz and 10 kHz. The hearing sensitivities of depigmented Proteus and black Proteus were compared. The highest sensitivities of the depigmented animals (N=4) were at frequencies 1.3-1.7 kHz and it was 2 kHz in black animals (N=1). Excellent underwater hearing abilities of Proteus are sensory adaptations to cave habitat.

Morphologic changes in the inner ear of Chinchilla laniger after middle ear administration of gentamicin in a sustained-release vehicle.

The use of transtympanic gentamicin has become a popular method of treating Meniere's disease; nevertheless, many questions still remain regarding this therapy. Until investigators can control the exact amount of medicine that is administered to the ear and have an understanding of the kinetics of gentamicin, therapy will continue to rely on empirical data. Previously we described the use of a fibrin-based sustained-release vehicle impregnated with gentamicin in the middle ears of chinchillas. With this model a kinetics curve of gentamicin was defined. The inner ears of these animals were submitted for immunohistochemical and histologic analysis. We discuss the ultrastructural changes seen and correlate this to our kinetics data. We also examine measurement of hair cell damage with heat shock protein levels. By better understanding the actions of gentamicin in this animal model, we hope to facilitate safer use of intratympanic medicines in our patient population.

[Comparison of vulnerability between avian and mammalian inner ears--electrophysiological and morphological studies].

In order to assess the vulnerability of the inner ear, auditory function and morphology of the inner ear were compared between adult budgerigars and adult guinea pigs. Budgerigars have been considered to have an excellent auditory-vocal system. Two experimental conditions were produced in each species; one by acoustic hyperstimulation (1500 Hz, 120 dBSPL) for 96 hours, the other by administration of kanamycin (200 mg/kg) for 7 weeks. Measurement of auditory evoked potentials (AEP) and observation of hair cells by electron microscopy were performed both immediately and 14 days after exposure. In the acoustic hyperstimulation experiment, AEPs of budgerigars showed less damage and better recovery than those of guinea pigs, probably because of morphological differences between the two species in hair and supporting cells. Electron microscopic observation on the budgerigars showed that a small part of the hair cell area was damaged and that regeneration of hair cells had occurred in this area 14 days after exposure. Such observations in guinea pigs revealed that outer hair cells had been damaged and replaced by supporting cells 14 days after exposure. In the kanamycin administration experiment, AEPs showed the same degree of damage and recovery in both species. This suggests that blood supply and drug transport to the inner ear are almost the same although the structure of the inner ear differs markedly between the two species. Electron microscopic observation did not show an apparent regeneration of hair cells 14 days after administration in the budgerigars. Guinea pigs had a tendency to show progressive damage of both auditory function and inner ear morphology even after the cessation of administration. Regeneration of hair cells in the budgerigar differed under both experimental conditions, suggesting that there is a difference in the mode of auditory disturbance between acoustic hyperstimulation and administration of kanamycin. In conclusion, resistance to acoustic hyperstimulation is higher in the avian inner ear than in the mammalian inner ear, while resistance to administration of kanamycin does not differ significantly between the two species.

[Experimental studies on the effect of labyrinth anesthesia]. / Experimentelle Untersuchung über die Wirkung der "Labyrinthanästhesie".

Injection of tetracaine into the tympanic cavity inhibits, independently of histologic lesions of the round window membrane, the active electrogenic pump in the stria vascularis cells. The DC potential in the endolymph is reduced with increasing doses of tetracaine, while the K+-Cl- activity is unchanged for 120 min. This drug does not alter the permeability of Reissner's membrane. Near the stria vascularis area, the oxygen pressure in the endolymph increases significantly after the effects of 4% tetracaine.

Effects of loud tones on the inner ear: a combined electrophysiological and ultrastructural study.

Guinea pigs were exposed to a 10 kHz pure tone and damage to the cochlea was investigated immediately after exposure, or after a recovery period ranging from 18-25 days. Structural damage was assessed using scanning electron microscopy and functional damage estimated using the N1 threshold audiogram. Exposure at 106 dB for 1 h caused obvious abnormalities of outer hair cell stereocilia. The location and extent of this damage was related to the immediate or long term deficits in the N1 threshold audiogram.