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PubMed1995

Combined effects of adrenalectomy and noise exposure on compound action potentials, endocochlear potentials and endolymphatic potassium concentrations.

The effects of removal of endogenous corticosteroids via bilateral adrenalectomy in combination with noise exposure (30 min at 100 dB) were determined by recording compound action potential (CAP) and endocochlear potentials (EP), and by measuring potassium concentrations (K+e) within the endolymph. Thirty-eight Long-Evans rats were divided into groups according to experimental treatments: adrenalectomy (ADX) or non-ADX and noise exposure or non-noise exposure. CAP thresholds, EP and K+e values were subjected to repeated-measures analysis of variance with group and time as factors classifying the measurements. Noise exposure resulted in significant elevations of CAP thresholds in both the ADX and non-ADX animals, but had no effect on either EP or endolymphatic K+e. Recovery was noted during all post-exposure measurement periods and was significantly faster for ADX animals. EP and K+e did not change during or after noise exposure. ADX animals showed a non-significant reduction of EP and a statistically significant increase of K+e during all measurement periods as compared to non-ADX animals.

Acoustic Stimulation↗
PubMed1995

NG-methyl-L-arginine protects the guinea pig cochlea from the cytotoxic effects of pneumolysin.

Sensorineural hearing loss is a major sequela of the bacterial meningitis associated in particular with Streptococcus pneumoniae. Recent studies have shown pneumolysin, a toxin elaborated by S. pneumoniae, to be cytotoxic to the guinea pig cochlea. The mechanisms of this cytotoxicity are, however, not fully understood. In the present study this deleterious action of pneumolysin has been shown to be blocked by pretreating the cochlea with NG-methyl-L-arginine, a known inhibitor of nitric oxide synthesis. Furthermore, pretreatment of the cochlea with MK-801, an NMDA receptor antagonist, was also found to confer marked protection from the action of pneumolysin. This latter finding is consistent with previous reports that excess stimulation of NMDA receptors within the cochlea, an event known to lead to excess nitric oxide release, have similar effects on the cochlea as pneumolysin perfusion. It would therefore appear that nitric oxide may represent a significant link in the chain of events leading to the deafness of bacterial meningitis.

Action Potentials↗
PubMed1996

[Suppression of spontaneous AC potentials in guinea pig cochlea by external tones].

Spontaneous electrical oscillations (AC potentials) were observed in the cochlea of three guinea pigs without any exposure to noise or drugs. The AC potentials disappeared completely within one minute after the cessation of artificial ventilation, and were suppressed by presenting external tones to the ear. As the frequency of the external tone was displaced toward that of the spontaneous oscillation, the signals were increasingly suppressed. Exposure to intense tone produced residual suppression of the AC potentials for several minutes. The time course of recovery from the suppression appeared to be similar to that in the noise induced temporary threshold shift measured psychoacoustically. From these results, it was concluded that the spontaneous AC potentials in the guinea pig cochlea were generated by the active mechanical vibration system at the area on the basilar membrane where the characteristic frequency corresponded to that of the AC potentials.

Acoustic Stimulation↗
PubMed2005

The effect of BAPTA and 4AP in scala media on transduction and cochlear gain.

We have injected by iontophoresis 4-amino-pyridine, a K+ channel blocker and BAPTA, (a Ca++ chelator), into scala media of the first three turns of the guinea pig cochlea. We measured the reduction in outer hair cell (OHC) receptor current, as indicated by cochlear microphonic measured in scala media evoked by a 207 Hz tone, and compared this with the elevation of the cochlear action potential (CAP) threshold. We found that in the basal turn, for frequencies between 12 and 21 kHz, CAP threshold was elevated by about 30 dB, while in the second turn, at the 3 kHz place, the maximum elevation was 15 dB. In the third turn, iontophoresis of 4AP and BAPTA reduced CM by similar amounts to that in the basal and second turn, but caused negligible elevation of CAP threshold. We conclude that the gain of the cochlear amplifier is maximal for basal turn frequencies, is halved at 3 kHz, and is reduced to close to one for frequencies below 1 kHz (no active gain). The effect of 4AP and BAPTA on neural threshold and the receptor current represented by CM may be explained by their action on OHC transduction without the involvement of IHCs.

4-Aminopyridine↗
PubMed1993

Changes in cochlear oxygenation, microcirculation and auditory function during prolonged general hypoxia.

Changes in cochlear microcirculation and oxygenation and auditory function were examined in anesthetized guinea pigs during prolonged hypoxic ventilation (8% oxygen in nitrogen) for 1 h. Cochlear blood flow and perilymphatic oxygen partial pressure were measured using laser Doppler flowmetry and oxygen-sensitive microelectrodes. Auditory function was examined by recording cochlear microphonics, compound action potentials and auditory evoked brainstem response. Blood pressure and heart rate were monitored. During systemic hypoxia, the perilymphatic PO2 dropped on average to about 70% of the initial value. Cochlear and brainstem potentials showed a mean reduction to 75-82%. Different effects of hypoxia on cochlear blood flow were observed and included decreases as well as increases. Mean arterial blood pressure declined significantly during hypoxia, while the heart rate remained constant. The changed variables returned to normal during reventilation with room air. The findings are discussed with regard to their significance as an animal model for the study of hypoxia-induced cochlear pathophysiology.

Action Potentials↗
PubMed2002

Caffeine and ryanodine demonstrate a role for the ryanodine receptor in the organ of Corti.

The hypothesis that the release of Ca(2+) from ryanodine receptor activated Ca(2+) stores in vivo can affect the function of the cochlea was tested by examining the effects of caffeine (1-10 mM) and ryanodine (1-333 microM), two drugs that release Ca(2+) from these intracellular stores. The drugs were infused into the perilymph compartment of the guinea pig cochlea while sound (10 kHz) evoked cochlear potentials and distortion product otoacoustic emissions (DPOAEs; 2f(1)-f(2)=8 kHz, f(2)=12 kHz) were monitored. Caffeine significantly suppressed the compound action potential of the auditory nerve (CAP) at low intensity (56 dB SPL; 3.3 and 10 mM) and high intensity (92 dB SPL; 10 mM), increased N1 latency at high and low intensity (3 and 10 mM) and suppressed low intensity summating potential (SP; 10 mM) without an effect on high intensity SP. Ryanodine significantly suppressed the CAP at low intensity (100 and 333 microM) and at high intensity (333 microM), increased N1 latency at low intensity (33, 100 and 333 microM) and at high intensity (333 microM) and suppressed low intensity SP (100 and 333 microM) and increased high intensity SP (333 microM). The cochlear microphonic (CM) evoked by 10 kHz tone bursts was not affected by caffeine at high or low intensity, and ryanodine had no effect on it at low intensity but decreased it at high intensity (10, 33, 100 and 333 microM). In contrast, caffeine (10 mM) and ryanodine (33 and 100 microM) significantly increased CM evoked by l kHz tone bursts and recorded from the round window. Caffeine (10 mM) and ryanodine (100 microM) reversibly suppressed the cubic DPOAEs evoked by low intensity primaries. Overall, low intensity evoked responses were more sensitive and were suppressed to a greater extent by both drugs. This is consistent with the hypothesis that release of Ca(2+) from ryanodine receptor Ca(2+) stores, possibly in outer hair cells and supporting cells, affects the function of the cochlear amplifier.

Action Potentials↗
PubMed1986

Offset tuning curves generated by simultaneous masking are more finely tuned than those generated by forward masking.

The rapid ending of a tone produces an evoked potential which has different properties than that which is produced by the sudden onset of a tone. At the level of the round window, the offset N1 N2 follows the ending of the cochlear microphonic (CM) by approximately the same amount of time as does the onset N1 N2 to the onset of the CM. Both onset and offset responses are abolished with cochlear lesion. Continuous masking was used to generate tuning curves (TCs) from the NI-PI component of the evoked potential recorded from the round window of the gerbil. Those evoked potentials generated in response to the tone onset were complementary in appearance to those generated in response to the tone offset. TCs generated by continuous masking of the NI-PII component of the auditory brainstem response (ABR) of the gerbil show the same pattern. When it is generated by simultaneous masking, the midfrequency offset TC in the gerbil and mouse is W-shaped. It has two well tuned tips which occur at frequencies below and above that of the probe stimulus used to generate the TC. It also has an even better tuned peak occurring at or slightly above the probe stimulus frequency, which becomes sharper as the masker sound pressure level (SPL) is increased from 50 to over 80 dB. Because the midfrequency onset response is approximately 40 dB lower than the midfrequency offset response, probe stimuli for onset TCs are generally set at lower SPLs. When the onset probe stimulus is set to the same level as that of the offset probe, the Q10 dB of the offset TC may be up to 10 times the value of the Q10 dB of the onset TC. The offset TC generated in the CBA/J mouse by forward masking is quite different from that produced by simultaneous masking. Both forward and simultaneous conditions utilized a 40 ms duration tone to mask the PI-NI component of offset and onset ABRs of the mouse which were evoked by a 10 ms duration, 32 kHz tone, presented at an interstimulus interval of 160 ms. Forward masking (when compared with simultaneous masking) resulted in a more sharply tuned onset TC. But the offset TC was much less sharply tuned in the forward masking condition. This suggests that the offset response may reflect functions which are involved with fine tuning at moderate to high intensities in the presence of simultaneous sounds of similar spectral characteristics.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Permeability to sodium ions of the endolymph-perilymph barrier.

The endocochlear potential and Na+ activity in the endolymph were simultaneously measured with a double-barreled Na+ selective liquid membrane electrode. The modified Na+ conductance and permeability coefficient of the endolymph-perilymph barrier were calculated from the rate of change in the endolymph Na+ concentration relative to the Na+ electrochemical gradient across the barrier during permanent anoxia. In normal guinea pigs the Na+ conductance of the endolymph-perilymph barrier is approximately 5 times less than its K+ conductance. Exposure to noise or treatment with kanamycin suppresses the cochlear microphonics but does not result in significant alterations in the Na+ permeability of the endolymph-perilymph barrier. It is likely that the Na+ permeability of the endolymph-perilymph barrier is not involved in the physiological processes which lead to the cochlear damage produced by noise or kanamycin.

Action Potentials↗
PubMed1996

Ciliary neurotrophic factor antagonizes gentamicin-induced alterations of electric potentials in auditory pathway in guinea pigs.

AIM: To study the effects of ciliary neurotrophic factor (CNTF) on the expressions of gentamicin ototoxicity in guinea pigs. METHODS: The auditory function of pigmented guinea pigs was examined using auditory brainstem response (ABR), cochlea microphonic potential (CM), and action potential of auditory nerve (AP). RESULTS: In animals injected gentamicin (80 mg.kg-1.d-1, i.m.), ABR threshold began to elevate on d 20, and prolongations of ABR wave I, IV and the I-IV interpeak latencies were observed. The animals treated with gentamicin for 30 d displayed lower amplitudes of CM and AP (N1) than the controls. CNTF (0.44 mg.kg-1.d-1, s.c.) inhibited the gentamicin-induced elevation of ABR thresholds, the prolongation of ABR wave I, IV and the I-IV interpeak latencies, and the decreases in amplitudes of CM and AP (N1). CONCLUSION: CNTF attenuated the gentamicin-elicited auditory impairment in guinea pigs.

Action Potentials↗
PubMed1992

Effects of organic acids on stria vascularis ultrastructure and function in the chinchilla.

The purpose of this study was to compare the effects of several organic acids (probenecid, sodium salicylate and penicillin G) on the endocochlear potential (EP) and the ultrastructure of the stria vascularis of the chinchilla with the effects of furosemide on these parameters. Chinchillas received 50 mg/kg i.v. doses of probenecid, sodium salicylate or penicillin G, or 25 mg/kg i.v. furosemide. The EP was monitored continuously before and for 60 min afterwards. The stria vascularis was removed at 10-min intervals from animals and from 10 to 60 min after the injection of these agents. Specimens were then processed for transmission electron microscopy. Only furosemide had an effect on the EP, causing a reversible reduction. The reduction of the EP was accompanied by the appearance of edema in the intercellular spaces of the stria vascularis. No significant edema was found after probenecid, sodium salicylate or penicillin G. This was consistent with the finding that none of these latter three agents affected the endocochlear potential.

Animals↗
PubMed1981

Narrow-band analysis of compound action potentials for several stimulus conditions in the guinea pig.

Compound action potentials (AP) were recorded under various stimulus conditions in 31 guinea pigs. Stimulus attenuation, decrease of inter-stimulus interval, increase of the level of a continuous wide-band noise maker, and lowering the animal's temperature all resulted in a drop of the AP amplitude and an increase in latency. A narrow-band analysis of the compound APs makes it possible to describe these AP changes in terms of the response behaviour of small cochlear regions according to their central frequencies. The results show that intensity-dependent changes in the AP parameters can be explained on the basis of the tuning properties of the auditory nerve fibres when the effect of the rise time of the tone-burst stimulus is taken into account. Shortening of the inter-stimulus interval produces a complex interaction in terms of tone-burst frequency and the region along the cochlear partition that contributes dominantly to the AP. It is concluded that response contributions from the narrow bands with a central frequency near the tone-burst frequency show the most adaptation. The change in amplitude for narrow-band responses under increased masking is similar to that for stimulus attenuation. It seems, however, that the underlying masking mechanism is more comparable to the adaptation mechanism. Cooling of the animal did not affect the sharpness of tuning. In all four recording situations there seems to be a decrease in the amount of synchronization of single-fibre responses as reflected in the width of narrow-band action potentials.

Acoustic Stimulation↗
PubMed1998

Protective effects of a neurotrophic ACTH(4-9) analog on cisplatin ototoxicity in relation to the cisplatin dose: an electrocochleographic study in albino guinea pigs.

Cisplatin is a potent cell cycle non-specific chemotherapeutic agent that produces side effects including high-frequency hearing loss. Hamers et al. (1994) studied electrophysiologically the effect of an ACTH(4-9) analog, also known as ORG2766, on the ototoxicity of cisplatin (administered at 2 mg/kg/day for 8 days) in guinea pigs. ORG2766 was given concomitantly with cisplatin during the 8 day period and an additional dose was given on day 9. The conclusion of this study was that ORG2766 might partially prevent cisplatin ototoxicity, but that the chosen cisplatin dose (2 mg/kg/day; 8 days) might have been too high. Because of the high cisplatin dose the protective power of the co-treatment with ORG2766 might not have stretched to all animals. In this study the results of co-treatment with the same dose and daily schedule of ORG2766 and cisplatin doses of 1.0 mg/kg/day and 1.5 mg/kg/day for 8 days are presented. The measurements were performed over a broad range of frequencies (0.5-16 kHz). Electrocochleography was performed at day 10. In the 1.0 mg/kg/day group there was no beneficial effect of ORG2766, although a tendency towards a division between a subgroup resembling control animals and a subgroup with severe cisplatin effects was noted in the co-treated group. In the 1.5 mg/kg/day co-treated group three animals showed compound action potential (CAP) amplitudes close to those of the controls at all frequencies except the very highest (12 and 16 kHz), the remaining three had CAP amplitudes comparable to those of animals in the cisplatin alone group. The effect of ORG2766 on the latter group of six animals taken together was statistically significant. The dichotomy in the results for the 1.5 mg/kg/day group co-treated with ORG2766 suggests that ORG2766 may have a protective effect against cisplatin ototoxicity which, however, depends on a factor currently unknown.

Action Potentials↗
PubMed1992

Bilateral electrocochleographic findings in unilateral Menière's disease.

At present, electrocochleography is the only proven investigation that can demonstrate objectively the presence of endolymphatic hydrops. The electrophysiologic recordings in response to sound stimuli show an enhancement of the negative summating potential in these cases. It is well established that patients with unilateral Meniere's disease have a high likelihood of development of the disease bilaterally in the fullness of time. Using transtympanic electrocochleography in 40 patients who manifested unilateral clinical Meniere's disease, we have recorded bilateral abnormalities indicative of endolymphatic hydrops in 35% of cases. The early recognition of incipient Meniere's disease in the asymptomatic contralateral ear of a patient with known unilateral disease has obvious profound implications for patient management.

Action Potentials↗
PubMed2001

Perilymphatic application of cisplatin over several days in albino guinea pigs: dose-dependency of electrophysiological and morphological effects.

Cisplatin, at 0, 3, 30 or 300 microg/ml in saline, was applied to the scala tympani of the cochlea of guinea pigs via osmotic mini-pumps, operating at a pump rate of 0.5 microl/h. Electrocochleographic recordings were made from an implanted round window electrode. When an electrocochleographic criterion of ototoxicity was reached (40 dB loss in compound action potential (CAP) threshold at 8 kHz), or after 1 week if this criterion was not reached, the animals were sacrificed for light microscopy. A subgroup of animals had endocochlear potentials (EPs) measured prior to sacrifice. Hearing remained stable in the 0 microg/ml control group, but a sudden drop of auditory sensitivity across the whole frequency range was observed in all other groups. It took 1-5 days before the drop occurred, dependent on cisplatin concentration. CAP and cochlear microphonics were lost simultaneously. The EP was severely depressed in the affected animals, suggesting that cisplatin effects on the EP are primary. However, histology revealed an accompanying loss of outer hair cells, primarily in the basal turn. It is concluded that if cisplatin is given until ototoxicity becomes apparent electrophysiologically, then the cochlear pathology from intrascalar cisplatin administration resembles that from daily parenteral administration at 1.5-2.0 mg/kg. The cochlear pathology from the parenteral treatment was greater than that observed with 30 microg/ml pumps, and less than that from 300 microg/ml pumps.

Action Potentials↗
PubMed1996

Effects of kainic acid on the cochlear potentials and distortion product otoacoustic emissions in chinchilla.

In absence of acoustic stimulation, the auditory nerve generates electrical noise with a spectral peak between 300 and 3000 Hz (Dolan et al., 1990). This electrical noise is eliminated when the dendrites of auditory nerve fibers are damaged by kainic acid (KA). We hypothesized that the KA-induced damage to the afferent dendrites might alter cochlear micromechanics or modify outer hair cell (OHC) electromotility. The KA-induced decrease in spontaneous electrical noise from the auditory nerve could conceivably reduce the spontaneous sounds recorded in the ear canal and the postulated change in cochlear micromechanics might alter distortion product otoacoustic emissions (DPOAE). To evaluate these hypotheses, we applied KA to the round window of the cochlea. KA reduced the spontaneous electrical noise recorded from the round window and significantly reduced the amplitude of the compound action potential (CAP) to tone bursts at 2, 4 and 8 kHz. KA caused only a slight reduction in the amplitude of the cochlear microphonic (CM) recorded from the round window: however, it had no effect on the spontaneous acoustic noise in the car canal or on 2 f1-f2 DPOAEs. These results suggest that the KA-induced reduction of electrical noise from the auditory nerve has no measurable effect on OHC electromotility as reflected in spontaneous otoacoustic emissions and that damage to the afferent dendrites has no effect on cochlear micromechanics as reflected in DPOAEs.

Acoustic Stimulation↗
PubMed2001

Masking by harmonic complexes in birds: behavioral thresholds and cochlear responses.

Thresholds for pure tones embedded in harmonic complexes were measured behaviorally and physiologically for three species of birds, and physiologically in gerbils. The harmonic maskers were generated using the Schroeder-phase algorithm, characterized by monotonically increasing or decreasing phase across frequency. Previous work has shown that these stimuli produce large differences in masking in humans but not budgerigars. In this study, we show that for two additional species of birds, the patterns of masking were similar to those shown for budgerigars, with masking differing only slightly for the two Schroeder-phase waveforms, and in the opposite direction from that demonstrated in humans. Amounts of masking among species corresponded qualitatively to differences in their critical ratios. Evoked potential measurements in birds and gerbils indicated responses that were consistent with the behaviorally measured thresholds in birds and humans. Results are interpreted in light of differences in frequency selectivity and cochlear temporal processing across species.

Acoustic Stimulation↗