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Histochemical, microchemical (microprobe) and organ culture approaches to the study of auditory development.

Cochlear development has been studied by means of biochemistry/histochemistry (Na+/K+-ATPase, adenylate cyclase, 2-deoxy-D-glucose and phospholipids), the energy dispersive X-ray microanalysis technique and organ culture of the mammalian inner ear. A high level of Na+/K+-ATPase and adenylate cyclase occurs in the stria vascularis and has been cytochemically demonstrated at the contraluminal side of marginal cell membranes. An increase in the adenylate cyclase content occurs approximately one day before and in parallel with the rise of the potassium content in endolymph. These processes are preceded by an ultrastructural differentiation of the stria vascularis but appear prior to the rapid increase of the endolymphatic potential. The functional activity of the developing/differentiating cochlea is reflected by increased levels of 2-deoxy-D-glucose first during the postnatal morphologic maturation of the organ of Corti and the stria vascularis approximately 1 week after birth, and, later during the maturation of cochlear potentials 10-14 days after birth. Organ culture of the embryonic inner ear is a suitable tool for studies on early (embryonic) morphologic development, neural induction, fate-mapping, epithelio-mesenchymal interactions and neurotrophic interactions. Concerning postnatal inner ear structures, organ culture has focused on development of afferent nerve fibres. The isolated organ is deprived of efferent fibres of central origin.

Adenosine Triphosphatases↗

Endocochlear potential and potassium concentration in endolymph and perilymph of the chinchilla.

Guinea pigs and chinchillas were studied for EP and potassium concentrations in scala media and scala tympani using potassium-sensitive microelectrodes. Response of EP to 3 min anoxia was strikingly different in these two species. On the other hand, the resting values for EP and potassium concentrations in endolymph and perilymph were not significantly different. These findings suggest that the different response to anoxia in these two species is due to differences in permeability of the cochlear partitions to the ions.

Animals↗

Auditory evoked responses in awake rabbits after exposure to high intensity noise impulses.

Impulse noise effects were tested in chronic experiments on 8 awake rabbits. Alterations of cochlear potentials and evoked responses from the inferior collinulus and the medial geniculate body were studied. The rabbits were subsequently exposed to 10 noise impulses of 144 dB SPL, then (after recovery) to 10 impulses of 153 and 164 dB SPL. After exposure the amplitudes of all potentials were reduced. Time of restitution depended on the intensity of the noise, the restitution failed after exposure to 164 dB SPL impulses. Time lapses of the amplitude-reduction and restitution process were comparable for both structures of the auditory pathway. The peak latencies were prolonged significantly in only two of the rabbits after this impulse intensity. Impulses of 164 dB SPL were followed by irreversible changes of all evoked responses.

Acoustic Stimulation↗

Response of cochlear potentials to presumed alterations of ionic conductance: endolymphatic perfusion of barium, valinomycin and nystatin.

Two models ('single-pump' and 'two-pump') of transepithelial potassium movement by the marginal cells of the stria vascularis have been proposed in the literature. Their validity was considered by exposing the endolymphatic (luminal) surface to agents (barium, valinomycin and nystatin) which are known to alter specific cellular membrane conductances in other tissues. This was accomplished by the use either of injections or of a relatively satisfactory technique for perfusion of scala media, which is described. Injection of barium caused the endocochlear potential (EP) to increase in normal animals and had no effect on the EP of deaf, Waltzing guinea pigs. Perfusion of the ionophores caused a decline in the EP in both normal and Waltzing guinea pigs. Only the 'two-pump' model (Na/K-ATPase-mediated cation pump on the basolateral membrane and rheogenic K transporter at the luminal membrane) is consistent with the results. The cellular heterogeneity of the cochlear duct, however, introduces a measure of uncertainty into this interpretation.

Animals↗

Comparison of current waveforms for the electrical stimulation of residual low frequency hearing.

Many cochlear prostheses employ charge-balanced biphasic current pulses. These pulses have little energy at low frequencies resulting in limited stimulation of low frequency hearing by mechanical responses to the electrical stimulus. However, if electro-mechanical transduction within the cochlea is nonlinear, electrical stimulation with asymmetric, charge-balanced current pulses may result in a mechanical response with significantly more low frequency energy. We estimated the mechanical response at low frequencies to pulsatile electrical stimulation of the cochlea. The auditory nerve compound action potential evoked by low frequency tones was forward-masked by a train of symmetric or asymmetric current pulses. Masking by asymmetric current pulses was not significantly different from masking by symmetric pulses matched for pulse duration and charge. In conclusion, there appears to be no advantage to using asymmetric current pulses for the mechanical stimulation of residual low frequency hearing by electrical stimulation of the cochlea.

Animals↗

Velocity and displacement coupling of mammalian inner hair cells and the mechanical resonance of the free-standing stereocilia.

Some controversy still exists as to whether the inner hair cells of the mammalian cochlea respond to the velocity or displacement of the basilar membrane or to a combination of these over their operating frequency range. A comparison between the nonlinear properties of the receptor potentials within inner hair cells of the basal turn of the guinea pig cochlea and the potentials recorded within the scala media of the same animals for stimulus frequencies between 200 and 3,200 Hz provides evidence that these inner hair cells change from velocity sensitivity to displacement sensitivity at about 1,000 Hz. We infer from this that viscosity within the subtectorial space is high enough to preclude mechanical resonance of the freestanding stereocilia of these cells as a frequency-selective mechanism within the mammalian cochlea.

Acoustic Stimulation↗

Effects of rise time on simultaneously recorded auditory-evoked potentials from the early, middle and late ranges.

The view that the effects of stimulus rise time are qualitatively different for early brain stem components, middle latency components and late vertex components of the auditory-evoked responses was reexamined. The amplitudes and latencies of the brain stem response (Jewett's wave V), middle latency components Na and Pa, and vertex potentials P1, N1 and P2, evoked by tone burts of various rise times, were analyzed. Increases in rise time were associated with smaller peak amplitudes and longer peak latencies for all of the components measured. These effects were comparable in magnitude for all the components. The results are interpreted in terms of a delayed and less synchronized neural discharge from the cochlea as rise time is extended.

Adult↗

[Changes in endocochlear potential induced by potassium-channel blockers].

The effect of various potassium-channel blockers, 4-aminopyridine (4-AP), tetraethylammonium (TEA) and quinine, on the endocochlear potential (EP) was studied in perfused guinea pig inner ears. The fast K(+)-channel blocker, 4-AP, did not alter EP but changed its response model to intense noise exposure. While TEA and quinine significantly reduced the amplitude of negative component of EP (N-EP), comparing with a relatively smaller increase in general EP (G-EP). The results indicated the existence of different K(+)-channels with different physiological functions.

4-Aminopyridine↗

Effect of intravenous vasopressin on endocochlear potential and systemic blood pressure in the guinea pig.

The effects of intravenous arginine-vasopressin (AVP) on the endocochlear potential (EP) and systemic blood pressure (BP) were examined in the guinea pig. Intravenous AVP (10(-7) M) elevated BP significantly but did not change EP. AVP (10(-8) M) produced a significant decrease in the amplitude of EP but did not change mean blood pressure significantly. AVP at 10(-9) M did not affect EP or BP. These results suggest that intravenous AVP might have an inhibitory effect on EP.

Animals↗

Local effects of PAF in guinea-pig inner ear.

The effect of PAF-containing artificial perilymph at 10(-7) and 10(-8) M on the endocochlear potential (EP) was investigated in guinea-pigs. The inner ear was perfused and the EP recorded at the same time. The characteristic decline of the EP which is highly sensitive to all stimuli could be prevented by pretreating the animals with either ginkgolide B (BN 52,021) or BM 13,177 (Sulotraban). Less effective in preventing the EP decline was Daltroban (BM 13,505). The results are discussed with respect to an involvement of PAF in cochlear physiology and in the regulation of ion transport, respectively.

Animals↗

Mechanism of cisplatin ototoxicity: antioxidant system.

The dose and duration limiting toxic effects of cisplatin are ototoxicity and nephrotoxicity. While several studies have attempted to shed some light on the causes of nephrotoxicity, the reasons for ototoxicity induced by cisplatin are poorly understood. Therefore, this investigation was undertaken to delineate the potential mechanisms underlying cisplatin ototoxicity. The role of glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde levels, and antioxidant enzyme activities [superoxide dismutase, catalase, GSH peroxidase, and GSH reductase] were examined in cochlear toxicity following an acute dose of cisplatin. Male Wistar rats were treated with various doses of cisplatin. Pretreatment auditory brain stem evoked responses (ABR) were performed and then post-treatment ABRs and endocochlear potentials were also performed after three days. Acute cochlear toxicity (ototoxicity) was evidenced as elevated hearing thresholds and prolonged wave I latencies in response to various stimuli (clicks and tone bursts at 2, 8, 16 and 32 kHz) on ABRs. The endocochlear potentials were reduced (50% control) in cisplatin-treated rats as compared to control animals. The rats were sacrificed and cochleae isolated. The GSH, GSSG and malondialdehyde levels, and antioxidant enzyme activities were determined. Cisplatin ototoxicity correlated with a decrease in cochlear GSH [0.45 +/- 0.012 nmol/mg] after cisplatin administration compared to 0.95-012 nmol/mg in control cochleae (P < 0.05). Superoxide dismutase, catalase activities and malondialdehyde levels were significantly increased in the cochleae of cisplatin injected rats. Cochlear GSH-peroxidase and GSH reductase activity significantly decreased after cisplatin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reduction of acoustically-induced auditory impairment by inhalation of carbogen gas. I. Permanent noise-induced cochlear damage.

The possible beneficial effects of carbogen gas (95% O2/5% CO2) inhalation on noise-induced permanent cochlear impairment were investigated. Groups of guinea pigs were exposed to daily 3 1/2-hour presentations of 120 dB of broad-band noise in an atmosphere of either carbogen gas or normal air. Other groups received carbogen or normal air with a low intensity (50 dB) acoustic exposure. After a 30-day stabilization period each ear was examined electrophysiologically and histologically. Measures included a.c. cochlear potentials from 100 Hz through 20 kHz as well as counts of missing inner hair cells (IHCs) and outer hair cells (OHCs). Statistically significant improvement in the 1 microV isopotential function of the a.c. cochlear potential over all test frequencies and significant reduction in the number of missing IHCs and OHCs was found to result from inhalation of carbogen gas. Blood gas analysis demonstrated a rapid and marked elevation in arterial PCO2 and PO2 with a corresponding drop in pH to result from inhalation of carbogen. The vasodilating effects of increased arterial carbon dioxide tension are discussed in terms of current speculations regarding the role of vasoconstriction in noise-induced hearing loss.

Animals↗

Meniere's disease and the summating potential. II. Vestibular test results.

Results of electronystagmographic (ENG) position and bithermal caloric tests from patients with abnormally enlarged summating potentials (SPs) were compared with results from a unilateral weakness (UW)-matched ENG-comparison group and with a group of patients with unilateral cochlear deficits and dizziness but without enlarged SPs. The patients with enlarged SPs had significantly higher incidence of caloric UW on the involved side than did the patients with cochlear deficits but without enlarged SPs. Also, the patients with SP enlargement had a significantly higher incidence of directional preponderance toward the involved side than did either of the comparison groups. Across-group differences in position test results were predictable from the caloric test results, but these differences were not statistically significant.

Adult↗

Cochlear responses to dynamic click patterns in the guinea pig.

Fast cochlear adaptation, expressed as percent inhibition of the summed action potential, is studied from the guinea pig cochlea responses to click trains, ramps, and steps in both directions. The transition time function of adaptation to constant click trains does not depend on click strength, but rather on click interval. On the background of steady state adaptation, click steps produce only transient changes of the adaptive state, opposite to step direction. Compared to constant train stimulation, adaptation is enhanced by descending click ramps, and diminished or reversed (near threshold) by ascending ramps.

Acoustic Stimulation↗

The avian stapedius muscle. Influence on auditory sensitivity and sound transmission.

The influence of the solitary avian middle ear muscle, the m. stapedius, on auditory sensitivity and sound transmission was investigated in the domestic chicken, Gallus gallus. Electrophysiological recordings of inner ear microphonic potentials (MP) were made in order to determine the effects of calibrated, mechanically induced stapedius muscle (SM) tension changes on sounds reaching the auditory receptor cells. The maximum MP responses recorded during the pre-tension measurements were on the order of 200 microV and were linear (on a log-log scale) over a range of 40-100 dB SPL. Tension levels of 50-400 mN in the SM caused a reduction of up to 20 dB in the MP at frequencies throughout the auditory spectrum. It is concluded that the SM of Aves serves to protect the inner ear receptor cells against overstimulation. In addition to attenuating the amplitude of the MP response, SM tension changes caused significant changes in the phase of the signals reaching the inner ear. The magnitude of attenuation in the ipsilateral MP response to 200-400 mN of tension was found to be similar to the interaural attenuation that occurs when sound is transmitted to the ipsilateral ear from the contralateral ear via the intracranial passageway. The similarity in MP amplitude changes resulting from SM tension and intracranial transmission suggests that the SM may be involved in interaural interaction and thereby may aid in sound localization.

Animals↗

An electrophysiological study on the effect of laser irradiation of round window membrane in the guinea pig.

An argon laser beam was used to irradiate the round window in 17 guinea pigs. Each animal was examined electrophysiologically with an electrode placed on the round window (RW) membrane 3 or 30 days after the irradiation, after which the cochlea was examined morphologically. The RW membrane was found intact in 16 out of 17 animals. All potentials (SP, CM, CAP) were abolished in 8 of the 17 animals. Histologically, perforations of the basilar membrane and Reissner's membrane were observed in 7 of 8 cases. In 4 of the 17 cases, a small effect of irradiation was evident both physiologically and histologically. Significant elevation of thresholds was observed in the remaining 5 animals, where amplitudes of CM, +SP, and CAP decreased at all intensities. Varying degrees of membranous labyrinth destruction can be used without perforating the RW membrane by the present method.

Animals↗

[Acoustic nerve adaptation in chronic acoustic trauma].

The adaptation phenomenon of the the cochlear nerve in the highest frequency region was studied by means of electrocochleography in the group of 32 persons exposed to prolonged noise and with noise-induced, mild hearing loss (in the 4--6 kHz region) and in 19 persons under the same conditions of noise-exposure but, without any evidence of the hearing loss. The same investigations were performed in the group of 27 normal-hearing persons and non-exposed to noise. In the whole group of persons exposed to prolonged noise, disregarding their hearing condition the amplitude-decrease of the action potential of the cochlear nerve due to the adaptation procedure, was twofold in comparison to the non-exposed persons. The latency of this potential was longer in the whole group of exposed to noise persons than in the intact persons. It was presumed that this type of auditory nerve adaptation results infinitial, ultrastructural noise-damage within the basal turn of the cochlea. Basing on the obtained results it was postulated that the adaptation phenomenon in the highest-frequency region can serve as an indicator of early noise-induced malfunction of the cochlea which probably precedes the highest-frequency threshold elevation in conventional audiometry.

Adaptation, Physiological↗

Ultrasonic electrocochleography in guinea pig.

In order to obtain information about how ultrasonic stimuli are perceived (USP) in man, guinea pig cochleae were stimulated by bone conduction with frequencies (98.8 and 143.5 kHz) above the normal auditory field of this animal. The cochlear potentials recorded consisted of CM, SP and AP originating from the basal turn of the cochlea, and were found to be influenced by asphyxia, administration of ethacrynic acid, hypothermia and change of interstimulus interval. In addition, in kanamycin-treated animals the mean AP amplitude decreased to about one fourth of the normal value, and the mean AP latency increased significantly. These findings suggest that there is no special sense organ for the detection of USP but that such sounds activate hair cells in the basal turn of the cochlea.

Animals↗