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The effect of blood flow promoting drugs on cochlear blood flow, perilymphatic pO(2) and auditory function in the normal and noise-damaged hypoxic and ischemic guinea pig inner ear.

The effect of blood flow promoting drugs, such as hydroxyethyl starch (HES) either of low or high molecular weight (HES 70, HES 200), pentoxifylline, ginkgo biloba, naftidrofuryl and betahistine, and various combinations of the drugs was studied in unexposed and noise-exposed (broad-band noise, bandwidth 1-12 kHz, 106 dB SPL, 30 min) guinea pigs. The results were compared without therapy and placebo (isotonic saline, NaCl). The cochlear blood flow (CoBF) and the partial pressure of oxygen in the perilymph (PL-pO(2)) were continuously and simultaneously recorded over a period of 210 min. In addition, cochlear microphonics (CMs), compound action potentials of the auditory nerve (CAPs) and auditory brain stem responses (ABRs) were registered. Noise-induced hearing loss (NIHL) paralleled a decrease of PL-pO(2). Both were found to occur before evidence of reduced CoBF. PL-pO(2) and CoBF declined progressively post-exposure, while CMs, CAPs and ABRs showed no further deterioration or signs of recovery up to 180 min after cessation of noise. Treatment started 60 min post-exposure, respectively after 90 min, without manipulation in unexposed animals, and was then studied for a further 120 min. In unexposed animals, CoBF increased significantly during infusion of HES 70, HES 200, pentoxifylline and betahistine. NaCl, ginkgo biloba and naftidrofuryl did not alter CoBF. PL-pO(2) decreased significantly during infusion of all administered drugs and combinations, except for NaCl. CMs, CAPs and ABRs remained constant, with the exception of increased ABRs after infusion of HES 70 and HES 200. In noise-exposed animals, a sustained therapeutic effect on cochlear ischemia was achieved only by HES 200 and pentoxifylline. HES 70, betahistine and ginkgo biloba compensated cochlear ischemia only during infusion; however, 30-60 min after termination of therapy, no significant difference of values for CoBF was observed compared to the untreated noise-exposed groups. NaCl and naftidrofuryl showed no effect on CoBF. None of the applied drugs had a sustained compensatory effect on cochlear hypoxia. CMs, CAPs and ABRs improved significantly after HES 70, HES 200 and betahistine, resulting in partial recovery of CMs, and partial (betahistine) or even full (HES 70 and HES 200) recovery of CAPs and ABRs. In contrast, NaCl, pentoxifylline, ginkgo biloba and naftidrofuryl had no therapeutic effect on NIHL.

Animals↗

Effects of electrical stimulation of medial olivocochlear neurons on ipsilateral and contralateral cochlear responses.

Recent anatomical evidence has cast doubt on the interpretation of the neural elements involved in past experiments in which efferents were electrically stimulated. To separate effects produced by medial olivocochlear (MOC) efferents from effects produced by lateral olivocochlear (LOC) efferents, MOC efferents were selectively stimulated by an electrode in the region of the MOC cell bodies in cats. For comparison, efferents were also stimulated with an electrode in the fourth ventricle (OCB stimulation, previously called COCB stimulation). MOC stimulation and fourth-ventricle OCB stimulation both produced qualitatively similar results bilaterally in that auditory-nerve compound action potential (N1) and endocochlear potential were reduced, and cochlear microphonic (CM) was increased. Both efferent-induced changes were affected in similar ways by changes in shock parameters, and were blocked by strychnine. At low sound levels, the decrease in N1 amplitude was approximately equivalent to a shift (decrease) in sound level but the change in N1 latency was not. The ratio of the CM increase to the N1 sound-level shift was independent of shock level or location. MOC stimulation typically produced an N1 sound-level shift of 11-16 dB in the contralateral ear and 4-7 dB in the ipsilateral ear. The ratio of these shifts almost equals the ratio of MOC neurons which had cell bodies on the stimulating-electrode side. Previous results reported by others with 'UOCB stimulation' now seem attributable to excitation of uncrossed MOC efferents rather than to excitation of uncrossed LOC efferents as previously thought. There is no effect reported in the literature or seen by us which can definitely be attributed to LOC neurons. Fourth-ventricle OCB stimulation typically produced an N1 sound-level shift in both ears of 19-22 dB which is approximately the sum of the crossed and uncrossed MOC shifts. Considering also that many uncrossed-MOC fibers course close to the midline (i.e. near the stimulating electrode), it seems likely that fourth-ventricle OCB stimulation excites both crossed and uncrossed MOC efferents. Referring to such stimulation in the cat as 'COCB stimulation' is therefore inaccurate and may lead to wrong conclusions about the functional role of various components of the olivocochlear fibers.

Acoustic Stimulation↗

Effects of kynurenic acid as a glutamate receptor antagonist in the guinea pig.

Glutamate excitotoxicity is implicated in both the genesis of neural injury and noise-induced hearing loss (NIHL). Acoustic overstimulation may result in excessive synaptic glutamate, resulting in excessive binding to post-synaptic receptors and the initiation of a destructive cascade of cellular events, thus leading to neuronal degeneration and NIHL. The purpose of this study was to determine whether this apparent excitotoxicity can be attenuated by kynurenic acid (KYNA), a broad-spectrum glutamate receptor antagonist, and protect against noise-induced temporary threshold shifts (TTS). Guinea pigs were randomly assigned to three separate groups. Base-line compound action potentials (CAP) thresholds and cochlear microphonics (CM) were recorded. Group I was treated with physiologic saline as a vehicle control applied to the round window membrane that was followed by 110 dB SPL wide-band noise for 90 min. Group II received 5 mM KYNA followed by noise exposure, and group III received 5 mM KYNA alone without noise exposure. Post-drug and noise levels of CAP thresholds and CM were then obtained. Noise exposure in the control group caused a significant temporary threshold shift (TTS) of 30-40 dB across the frequencies tested (from 3 kHz to 18 kHz). Animals that received 5 mM KYNA prior to noise exposure (group II) showed statistically significant protection against noise-induced damage and demonstrated a minimal TTS ranging between 5 and 10 dB at the same frequencies. Animals in group III receiving KYNA without noise exposure showed no change in thresholds. Additionally, cochlear microphonics showed no considerable difference in threshold shifts when controls were compared to KYNA-treated animals. These results show that antagonizing glutamate receptors can attenuate noise-induced TTS, suggesting that glutamate excitotoxicity may play a role in acoustic trauma.

Animals↗

Inner ear structure and electrophysiological audiograms of the subterranean mole rat, Spalax ehrenbergi.

Subterranean mole rats of the Spalax ehrenbergi superspecies in Israel have a distinctly developed vocal repertoire, presumably compensating together with olfaction for their complete blindness, thus providing an efficient communication system underground. Here we describe the unique organization of the cochlea of Spalax among mammals. The cochlea is subdivided into different subsystems where in the apical subsystem the fluid space and the organ of Corti differ remarkably from that in the basal subsystem, a feature as yet unknown in other mammals. The audiograms based on cochlear microphonics and on evoked potential recordings from the midbrain and brainstem, reveal a hearing range from 0.1 kHz-10 kHz with a best sensitivity between 0.5 and 1 kHz.

Acoustic Stimulation↗

Asynchronous neural activity recorded from the round window.

Voltage recorded from an electrode on the round window (RW) of guinea pig has characteristics that reflect the activity of auditory-nerve fibers in the absence of acoustic stimulation. Fast Fourier transformation (FFT) of the noise recorded from the RW electrode shows a broad spectral peak from 0.8-1.0 kHz. The magnitude of the biological noise is increased by high-frequency, bandlimited acoustic noise stimulation. Pure tones can suppress or enhance the spectral components around 0.8-1.0 kHz depending on frequency and intensity. Kainic acid applied to the intact RW membrane eliminates the biological noise (and the evoked cochlear whole-nerve responses) without alteration of the cochlear microphonic or the summating potential. The spectral characteristics of the biological noise seem to be related to the elemental waveform contributed by the individual auditory-nerve fibers to the voltage recorded at the RW electrode [Kiang et al., Electrocochleography, edited by R. J. Ruben, C. Elbering, and G. Solomon (University Park, Baltimore, 1976)].

Animals↗

An electrophysiological study of the effects of acute methylmercury chloride exposure on the function of the guinea pig cochlea.

The inner ear function of methylmercury chloride (MMC)-exposed guinea-pigs was examined in this study. Previous studies which investigated the function of the eighth cranial nerve and Corti-organ using cochlear microphonics (CM), compound action potential (CAP) and measurement of endocochlear potential (EP) reported ototoxicity following experimental exposure to MMC. In this report, the effect of MMC on the cochlea and the eighth cranial nerve were investigated systematically by measuring CM, action potential (AP), EP and K+ ion concentration of the endolymph. Guinea-pigs were injected with 5 mg/kg MMC (using 0.2% solution) twice a week for 1-3 weeks. The maximum output voltage of AP was decreased by injection of MMC (5 mg/kg x 6). A decrease in the CM maximum output voltage and the elevation of CM pseudothreshold was seen after MMC injection. Changes in EP during 3 min anoxia were observed, especially a decrease in the absolute value of the negative potential. The endolymph K+ ion concentration remained unchanged. These findings indicate that the diffusion potentials decreased and at the same time was reduced the maximum output voltage in CM induced by MMC injection (5 mg/kg x 6) in this experiment.

Action Potentials↗

A comparison of extratympanic versus transtympanic recordings in electrocochleography.

Detection thresholds, amplitudes and input output curves of cochlear microphonics (CMs), and action potentials (APs) determined by extratympanic electrocochleography (ET ECochG) were compared with those determined by transtympanic (TT) ECochG in the same ears. Two groups were studied: 12 ears in 9 volunteers with normal hearing, and 6 ears in 6 subjects with sensorineural hearing loss. Short tone bursts with frequencies of 0.5, 1, 2 and 4 kHz were used as acoustic stimuli to evoke CMs, and a click was presented to measure the APs. In both groups, although the two approaches produced large differences in amplitudes, nearly identical values were obtained for the CM and AP detection thresholds. The CM and AP input-output curves obtained from mean amplitudes at each intensity in normally-hearing ears had similar slopes with the two approaches. These findings demonstrate the clinical usefulness of ET ECochG.

Adult↗

The effect of bacterial endotoxin upon the morphology of the tectorial membrane and stereocilia in the guinea pig cochlea.

Endotoxin of E coli was microperfused into scala tympani or injected into the cerebrospinal fluid in anaesthetised pigmented guinea pigs. The effects of endotoxin on the cochlea were studied using electrophysiological techniques and scanning electron microscopy. We found a drop in the amplitude of the cochlear microphonics and compound action potentials 2 to 2.5 hours after injection. There were also changes in the morphology of stereocilia and the tectorial membrane. The stereocilia lost their rigidity and the tectorial membrane appeared swollen. These effects were less severe in animals which were pretreated with dexamethasone.

Action Potentials↗

No change detected on distortion products in awake or anesthetized guinea pigs.

Two pure tones presented simultaneously to one ear can produce physiologically and perceptively other tones called distortion products which originate in the inner ear. Notable differences exist between their physiological and perceptive features. In physiological experiments the anesthesia may alter the functioning of the cochlea, especially its efferent system. Physiological measurements made of distortion products taken from the same animals under anesthesia or in the awake state were compared using round window cochlear microphonic responses and evoked potentials from the eighth nerve and the auditory cortex. The physiological measures appeared unaltered by anesthesia, but in both the awake and anesthetized states, repeated measuring at intervals of several minutes could show apparently random variations of a few decibels.

Acoustic Stimulation↗

[The meaning of nonlinear distortions in the internal ear for acoustic and ultrasonic stimuli].

A comparative study of nonlinear distortion of microphonic potentials in the rabbit cochlear at the air and bone conduction showed equal values for the air as well as for the within the ultrasonic frequency range did not exceed the hearing spectrum values. The hearing response to ultrasonic stimuli was found not to be due to formation of overtones of ower frequencies but to represent rather the direct cochlear response.

Acoustic Stimulation↗

Modulation at the guinea pig round window of summating potentials and compound action potentials by low-frequency sound.

Low-frequency sound was used to modulate responses to short single-frequency tone bursts at the guinea pig round window. Summating potentials (SP) increase (reach higher positive values) during the negative half-cycle of the low-frequency cochlear microphonic (LFCM) and decrease during the positive half-cycle of the LFCM. The compound action potential (AP) amplitude decreases during the negative half-cycle of the LFCM. The negative half-cycle of the LFCM can be identified with scala tympani displacement. SP modulation depth is defined as the difference between the highest and the lowest SP value found for tone burst stimulation at different phases of the low-frequency sound while the sound levels of the tone burst and the low-frequency bias are kept constant. When normalized with respect to the SP amplitude found without bias, the SP modulation depth is independent of the sound level of the tone burst in the range from 48 to 68 dB SPL. The normalized AP suppression tends to increase with decreasing tone burst sound level. A dynamic nonlinear mechanism which might explain these results is discussed. This mechanism is based on voltage-sensitive changes.

Acoustic Stimulation↗

The effect of intravenous injection of lidocaine on the auditory system.

Lidocaine hydrochloride was intravenously injected into guinea pigs. Auditory evoked brain stem response (ABR) to clicks, whole nerve action potential (AP) and summating potential (SP) to clicks and 4 kHz tone bursts, and cochlear microphonics (CM) to 4 kHz tone bursts were recorded during a 60 min period following injection. Injection of a small dosage of lidocaine (4 mg/kg body weight) failed to produce any significant change in ABR wave III, AP and CM. However, a large dosage of lidocaine (20 mg/kg) influenced ABR and AP, but had no observable effect on CM. Latency of ABR wave III was prolonged, but its amplitude remained unchanged. Change in the case of 4 kHz tone burst-evoked AP was more pronounced than that in the case of the click-evoked AP. The 4 kHz tone burst-evoked AP showed an initial increase in amplitude, which was followed by a gradual decrease. Latency of both click and 4 kHz tone burst-evoked AP did not show any changes. The amplitude of SP showed more variation during the course of the test period following lidocaine injection than did either ABR or AP, however, SP decreased in its amplitude approximately 60 min after lidocaine injection. Complete disappearance of ABR and AP, followed by recovery of ABR and AP, was observed in animals given a larger dose (30 mg/kg) of lidocaine. CM did not completely die out, and in fact sustained only about a 75% decay in its amplitude. From the above results, it should be concluded that lidocaine, when injected intravenously, affects ABR and AP significantly more than CM.

Action Potentials↗

Effects of acoustic overstimulation on cochlear evoked potentials.

Guinea pigs were exposed to 2 kHz pure-tone or octave-band pass noise at an intensity of 100 dBSPL for 30 min. The effects of sound exposure on cochlear microphonics (CM) and compound action potential (AP) were studied using a test condition devised to complete the measurement of the sensitivity of both potentials for the frequency from 1 to 7 kHz within several minutes. The loss of CM sensitivity was limited to around 5 dB for all test frequencies in animals exposed either to pure-tone or band noise. In contrast, the loss of AP in both exposure conditions was significantly greater than that of the CM, and the magnitude of the AP losses reflected the frequency characteristics of the exposure sounds. From these observations, the AP is considered to be a more sufficient index than the CM in studying the effects of acoustic overstimulation.

Animals↗

Are inner or outer hair cells the source of summating potentials recorded from the round window?

The relative contribution of inner hair cells (IHCs) and outer hair cells (OHCs) to the production of the summating potential (SP) is unresolved in the literature. Since OHCs in the base of the cochlea have been reported to produce little dc receptor potential except at very high sound pressure levels [I. J. Russell and P. M. Sellick, J. Physiol (London) 284, 261-290 (1983)], the IHCs appear to be the dominant source of the SP. However, results of intracochlear recordings are conflicting, although deriving from measurements in different turns of the cochlea [e.g., I. J. Russell and P. M. Sellick, J. Physiol. (London) 284, 261-290 (1983) versus P. Dallos and M. A. Cheatham, Sensory Transduction (1992)]. To determine which type of hair cells is the dominant source of the SP recorded at the round window, we used carboplatin to selectively destroy IHCs or a combination of IHCs and OHCs in the chinchilla. Related work, using measurements of distortion product otoacoustic emissions and cochlear potentials to assess the functional status of the OHCs served to validate this animal model [Trautwein et al., Hearing Res. 96(1-2), 71-82 (1996)]. The SP, cochlear microphonic (CM), and compound action potential (CAP) were recorded from the round window, and cochleograms were determined using well-established histological methods. The results were reasonably distinctive among three groups of ears--control (from untreated normal chinchillas), IHC-loss (extensive IHC loss with minor or no loss of OHCs), and IHC-OHC loss (total IHC loss plus extensive loss of OHCs over the basal half of the cochlea). Ears of chinchillas in the IHC loss group had a decrease of over 50% in SP output compared to control ears with the exact reduction depending somewhat upon the stimulus conditions. Ears in the IHC + OHC loss group, nevertheless, showed even further reduction in SP output which was clearly attributable to destruction of OHCs in the cochlear base. It was concluded that, although the IHCs are responsible for a greater contribution of dc-receptor potential to the SP recorded at the round window, a significant contribution is made by the OHCs, as well. The results suggest, specifically, that the round window "sees" SP output roughly in inverse proportion to the IHC:OHC. Lastly, the complexity of SP production, as recorded from the round window, precludes a completely straightforward interpretation of the SP:CAP in clinical ECochG.

Acoustic Stimulation↗

Pathophysiology of the ototoxicity of cis-diamminedichloroplatinum.

The electrophysiologic and histopathologic changes in the inner ear caused by the administration of cis-diamminedichloroplatinum (CP) were studied in guinea pigs. The endocochlear dc potential (EP) gradually decreased after the intravenous injection of CP and reached approximately 0 mV on the fourth day, but the EP did not become negative. The cochlear microphonics also diminished and could not be recorded on the fourth day. The negative potential of the organ of Corti remained in the normal range during the experiment. A large negative summating potential (SP) was observed one day after injection, but the amplitude of the negative SP became small on the second day. Light microscopic examination demonstrated that the outer hair cells are destroyed in the basal turn of the cochlea and are preserved in the upper turns, while the inner hair cells are almost completely preserved in all turns. The stria vascularis was found to be slightly atrophic. Severe collapse of Reissner's membrane was observed in the basal turn.

Animals↗

4-aminopyridine in scala media reversibly alters the cochlear potentials and suppresses electrically evoked oto-acoustic emissions.

Iontophoresis of 4-aminopyridine into scala media of the guinea pig cochlea caused elevation of the thresholds of the compound action potential of the auditory nerve, loss of amplitude of the extracellular cochlear microphonic response (CM), increase in the endocochlear potential (EP) and reduction in the amplitude of electrically evoked oto-acoustic emissions (EEOAEs). These changes were reversible over 10-20 min. The reciprocity of the changes in the CM and the EP was consistent with an interruption of both DC and AC currents through outer hair cells (OHCs), probably by blockade of mechano-electrical transduction (MET) channels in OHCs. Reductions in EEOAEs were consistent with the extrinsically applied generating current entering the OHC via the MET channels. Implications for the activation of OHC electromotility in vivo are discussed.

4-Aminopyridine↗

Ryanodine receptors and BK channels act as a presynaptic depressor of neurotransmission in cochlear inner hair cells.

Ryanodine receptors (RyRs) are known to contribute to the regulation of free cytosolic calcium concentration. This family of intracellular calcium channels plays a significant role in calcium-induced-calcium-release (CICR), and have been implicated in calcium-dependent processes requiring exquisite spatio-temporal regulation. In order to characterize the importance of these intracellular calcium channels in cochlear physiology, we perfused the guinea pig cochlea with antagonistic concentrations of ryanodine. The distortion products of the cochlear microphonic and the compound action potential of the auditory nerve were reversibly inhibited by ryanodine (IC(50)=27.3 microm, Hill coefficient=1.9), indicating an action at the cochlear amplifier. Single auditory nerve fibre recordings showed that ryanodine slightly increased spontaneous firing rates by 22%, suggesting an excitatory effect of ryanodine. This paradoxical effect could be explained by an inhibitory action of ryanodine on presynaptic BK channels of inner hair cells (IHC). Indeed, perfusing iberiotoxin also increased the spontaneous firing activity of the auditory nerve fibres. Furthermore, whole-cell patch-clamp recordings demonstrated that ryanodine inhibits BK currents at the IHC level. Conversely, immunohistochemistry demonstrated a strong expression of RyR in IHCs and, more particularly, below the cuticular plate where membranous BK channels are highly expressed. Overall, the study demonstrated a key role for RyR and CICR in signal transduction at the IHCs. We therefore propose that coupled RyR--BK channels act to suppress the fast neurotransmission in IHCs.

Action Potentials↗

The quivering mutant mouse: hereditary deafness of central origin.

Mice homozygous for the recessive quivering gene are largely unresponsive to sound, although their cochleas appear normal by light microscopy and cochlear hair cells do not degenerate with age. Cochlear potentials and inferior colliculus evoked responses were recorded in quivering mice (qv/qv) and in littermate controls (+/qv or +/+). There were no significant differences between mutants and controls in cochlear microphonic amplitudes or compound action potential thresholds, amplitudes and latencies. However, inferior colliculus evoked responses in mutants were small in amplitude and abnormal in waveform. Latencies were long and thresholds were elevated by at least 50 dB at all frequencies tested. These data suggest that the genetic hearing impairment in quivering mice is retrocochlear.

Action Potentials↗