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Cytotoxic effects on hair cells of guinea pig cochlea produced by pneumolysin, the thiol activated toxin of Streptococcus pneumoniae.

The cytolytic toxin, pneumolysin, from the gram positive bacterium, Streptococcus pneumoniae, when perfused through the scala tympani of the guinea pig cochlea reduced the amplitude of both the compound action potential and the cochlear microphonic potential. When the surface of the organ of Corti was examined by scanning electron microscopy, both inner and outer hair cells and supporting cells were found to be damaged. Inner hair cells and outer hair cells of row 3 were the most susceptible to damage by pneumolysin, followed by row 2 and then by row 1 of the outer hair cells. Damage to hair cells included disruption and splaying of stereocilia, loss of stereocilia and complete dissolution of hair bundles. Apical surfaces of hair cells and supporting cells were torn, pitted and cratered with shrinkage and tearing of cell boundaries. Within the dose range perfused (0.05-1 micrograms/microliters in a 10 microliters aliquot), the magnitude of the physiological and anatomical lesions was concentration dependent. The cytotoxic effects of pneumolysin reported here may be clinically significant factors in deafness caused by meningitis and otitis media in humans.

Animals↗

Non-specific effect of beettahistine on cochlear electrophysiology in guinea pig.

Beettahistine hydrochloride (BH) is reported to be beneficial in the treatment of certain type of vestibulo-cochlear disorders. Experimentally is shown that BH inhibits vestibular firing rate and improves cochlear blood flow by dilatating the larger feeding vessels. Both these effects are weak, and hardly can explain the clinical benefits reported for the drug. We investigated the effect of BH on the organ of Corti electrophysiology in vivo. Two microliters of 1, 2, 5 and 10% saline solutions of BH was applied (in increasing order) to the round window (RW) membrane in an anesthetized guinea pig (n = 5). Summating potential (SP), action potential (AP), and cochlear microphonics (CM) were recorded at 16 kHz frequency using RW Ag wire electrode. The repeated applications of BH with increasing concentrations produced a dose-dependent threshold shift in CAP. The I/O function for 20, 30, 40, 50, 60, 70, and 80 dB at 16 kHz indicated that there was a saturation before complete blockade of the responsiveness in all measured parameters. SP and CM changes nearly followed CAP changes. The changes recover during 2 hours follow-up period. Our findings indicate that BH affects the organ of Corti electrophysiology. That the drug effect saturates before a complete blockade suggests non-specific effect of BH on the organ of Corti structures and cochlear nerve.

Animals↗

[Inner ear physiological function and pathological morphology in the offsprings of sensorineural hearing loss female guinea pigs induced by homogeneous inner ear antigens immunizing].

OBJECTIVE: To explore if the autoimmune of anti-labyrinth tissues acts as one of pathogenic cause by observing the inner ear physiological functions and pathological morphology changes of offspring of autoimmune sensorineural hearing loss (ASHL) female guinea pig. METHODS: The pregnant guinea pigs were immunized with homogeneous inner ear antigens (HIEAg), then, the hearing function were measured with EcochG [inspecting items including acoustic nerve compound action potential (cAP), summation potential (-SP) and cochlear microphone potential (CM)], while the vestibular function were measured with electronystagmography (inspecting items including spontaneous nystagmus and caloric test), inner ear Celloidin section with haematoxylin-eosin dyeing and being inspected under light microscope. The special antibodies in serum and special lymphocyte immune reaction were measured with ELISA and 3H-TdR intermingling lymphocyte transform test in all female guinea pigs and their offspring guinea pigs. RESULTS: In 7 offspring guinea pigs, 3 animals appeared sensorineural hearing loss. Immuno-inflammation pathologic changes happened in the labyrinth (including the number of bipolar cells reduced and some kind of inflammatory cells infiltrated in spiral ganglion and endolymphatic hydrops et al.), and rise of special antibodies against HIEAg in serum. There were no any obvious abnormity found in non-ASHL pregnant and normal contrastive pregnant guinea pigs and their offspring. CONCLUSIONS: In this study, some of ASHL female guinea pig's offspring demonstrated different grades of sensorineural hearing loss and inner ear inflammation, and the special humoral and cellular immune reaction against HIEAg, which could be induced by autoimmune inflammation against inner ear tissues antigens with special antibodies (maybe including special cellular immune reaction) from matrix through placental barrier. This result suggests that the factor of autoimmune against inner ear tissue antigens may be one of pathogenic causes inducing non-heritage congenital sensorineural hearing loss.

Animals↗

Temporal distortion products (kernel slices) evoked by maximum-length-sequences in auditory neuropathy: evidence for a cochlear pre-synaptic origin.

When special pseudo-random stimuli sequences (maximum length sequences: MLS) are combined with a deconvolution analysis technique, it is possible to derive new evoked potential components that are called kernels. The kernels give a measure of the temporal interactions that take place between the responses to successive stimuli. This may provide an objective neurophysiological test for the exploration of a dimension of hearing which has hitherto been limited to psychophysical methods. Until now, auditory short-latency kernels obtained by the MLS method have been related to the late portion of the brainstem auditory evoked potential (BAEP), suggesting that temporal interactions occur rather late in the auditory pathways. We report 4 children without any BAEP neural components, who all retained isolated cochlear microphonic potentials. Three of them produced click-evoked otoacoustic emissions and two of them demonstrated only moderately impaired audiometric thresholds. This combination of absent BAEP neural components with preserved otoacoustic emissions and cochlear microphonic potential corresponds to a peculiar pattern of auditory dysfunction recently coined "auditory neuropathy'. All 4 children exhibited well-defined kernels at latencies consistent with the microphonic potential. These data indicate that the cochlea itself can generate kernels at a presynaptic level. They open up the question of the identification of the physiological site(s) responsible for the generation of MLS-evoked kernels.

Adolescent↗

Lysine and polylysine: correlation of their effects on polyphosphoinositides in vitro with ototoxic action in vivo.

Low concentrations of poly-L-lysine, a polycationic hydrophilic molecule, caused a large expansion of polyphosphoinositide monolayers and produced a significant loss of cochlear microphonic potentials in perilymphatic perfusions in the guinea pig. In contrast, the monomeric L-lysine had only slight effects on polyphosphoinositide monolayers and did not affect cochlear microphonic potentials even at concentrations as high as 10 mM. These data substantiate the hypothesis that the expansion of polyphosphoinositide monolayers by a drug is an indicator of its ototoxicity.

Animals↗

[Narrow-band action potentials of the guinea-pig cochlea as compared with the ordinary electrocochleograms under normal and pathological conditions].

The narrow-band action potentials (NAP) and the ordinary electrocochleograms were recorded from the guinea-pig cochlea under normal and pathological conditions in order to study whether the NAP could be a useful measure to detect cochlear dysfunctions. The cochlea damaged either by the administration of kanamycin or by a mechanical lesion of the round window served as pathological materials. Recordings showed that the threshold and amplitude measured for the N1 potential of NAPs ran in parallel with those of the cochlear microphonic potentials (CM), under both normal and pathological conditions of the cochlea. This implies that the CM could be replaced by the NAP when difficulties were present in recording CMs. It may be inferred that the NAP reflects responses of the inner hair-cells and cochlear nerves, while the CM would mainly be derived from responses of the outer hair-cells to the frequency-specific movements of the basilar membrane. If so, the NAP should offer a good means for the objective audiometry. Recording NAPs is also superior to the ordinary electrocochleography in that the method makes it possible to obtain responses generated near the apex of the cochlea, i.e., responses to low-pitch sound stimuli.

Action Potentials↗

Changes in cochlear mechanics during vocalization: evidence for a phasic medial efferent effect.

The mustached bat, Pteronotus p. parnellii, has a finely tuned cochlea that rings at its resonant frequency in response to an acoustic tone pip. The decay time (DT) and frequency of these damped oscillations can be measured from the cochlear microphonic potential (CM) to study changes in cochlear mechanics. In this report, we describe phasic changes that occur in synchrony with communication sound vocalizations of the bat. Three animals with chronically implanted electrodes were studied. During the experiments, 1-2 ms tone pips were emitted from a speaker every 200 ms. This triggered a computer analysis of the resulting CM to determine the DT and cochlear resonance frequency (CRF) of the ringing. The time relative to vocalizations was determined by monitoring the output of a microphone placed near a bat's mouth. Similar results were obtained from all three bats tested. In a representative case, the average DT was 2.33 +/- 0.25 ms while the bat was quiet, but it decreased by 46% to 1.26 +/- 0.75 during vocalizations, which indicates a greater damping of the cochlear partition. Sometimes, DT started decreasing immediately before the bat vocalized. After the end of a vocalization, the return to baseline values varied from rapid (milliseconds) to gradual (1-2 seconds). The CRF also changed from baseline values during vocalization, although the amount and direction of change were not predictable. When gentamicin was administered to block the action of medial olivocochlear (MOC) efferents, DT reduction was still evident during vocalization but less pronounced. We conclude that phasic changes in damping occur in synchrony with vocalization, and that the MOC system plays a role in causing suppression. Since suppression can begin prior to vocalization, this may be a synkinetic effect, mediated by neural outflow to the ear in synchrony with neural outflow to the middle ear muscles and the muscles used for vocalization.

Acoustic Stimulation↗

Effects of acoustic trauma on the cochlear potentials.

The cochlear microphonic, summating potential, and action potential were recorded from all three turns of the gerbil cochlea prior to and following a 1-h exposure to a high-intensity pure tone. Results proved that the depression in the cochlear microphonic was greater when recorded from the upper two turns of the cochlea. The losses for the summating potential were not dependent on recording location. Although the cochlear microphonic and to some extent, the negative summating potential, reflected locally generated activity from the hair cells, the positive summating potential appeared to be dependent on distant electrical activity.

Action Potentials↗

Sources of frequency following responses (FFR) in man.

In order to study the sources and pathways which are responsible for the frequency following response (FFR), records were made in control subjects and in patients with special types of lesion and response. It has already been shown that the FFR in normal subjects to tone bursts with single onset phases is made up of a short latency cochlear microphonic potential (CM) and a longer latency neural component (neural FFR). No neural FFR could be recorded in patients with upper brain-stem lesions (absence of click-evoked responses from the inferior colliculus along with clinical signs of such a lesion). Their FFR was exclusively a cochlear microphonic potential, thus demonstrating that the neural FFR with a latency of 6 msec is generated in the region of the inferior colliculus. Also in subjects with large post-auricular muscle (PAM) responses, the PAM can contribute to the FFR, with a latency of 10 msec. In patients with high-tone hearing loss due to acoustic trauma, no CM could be recorded while a neural FFR with a latency of 6 msec was present. This indicates that the CM recorded by this technique may be generated in the basal turn. It also demonstrates that the pathway of the neural FFR begins in the apical turn of the cochlea.

Adult↗

Fetal sheep in utero hear through bone conduction.

PURPOSE: Although the air-conduction pathway is the principal mode of sound transmission to the inner ear, this may not be true for the fetus in utero. The fetus detects and responds to sounds in the maternal environment. Exogenous sounds can reach the fetal inner ear through the ear canal and middle ear system, bone conduction, or both. This study was designed to compare the effectiveness of these two routes of sound transmission by recording cochlear microphonic potentials from the fetus in utero in response to airborne sounds. MATERIALS AND METHODS: Cochlear microphonics (CMs) recorded from one round window (RW) of fetal sheep in utero were obtained in three conditions: (1) head uncovered; (2) head covered with a neoprene hood; and (3) head covered with a neoprene hood fashioned with a hole that permitted the pinna and ear canal to be exposed. Tone bursts (0.5, 1.0, and 2.0 kHz) were delivered through a loudspeaker at high intensities (100 to 135 dB sound pressure level) to the flank of the ewe. CMs were detected with indwelling electrodes, amplified, and averaged. CM input-output functions were obtained from the fetus in each of the three conditions described above. RESULTS: CMs recorded with the head uncovered were more sensitive than were the CMs recorded with the hood in place. There was no difference in sensitivity between the condition during which the head was completely covered and the condition in which the pinna and ear canal are exposed. CONCLUSION: The principal mode of sound transmission into the fetal inner ear is through bone conduction.

Acoustic Stimulation↗

[Cochlear and retrocochlear deafness induced by immunity with different inner ear tissue antigens].

OBJECTIVES: To inquire into whether the different inner ear tissue antigens could cause different kind of hearing loss, and to find out the disorder positions of auditory system. METHODS: The basilar membrane (BM), spiral ligament (SL), and spiral ganglion (SG) of guinea pigs were removed for making antigens, respectively. Then, we used these antigens to immune guinea pigs. The special humour and cellular immune reaction, hearing function, and inner ear histopathological changes were observed. RESULTS: In BM-antigen and SL-antigen immune group, the various degrees of cochlear microphonic potential disturbance, recruitment, and immune pathological inflammation in cochlear duct and stria vascularis were found. In SG-antigen immune group, auditory nerve compound action potential changes were prominent, and the inner ear pathological damage mainly existed in cochlear axis vessels or surround areas, and SG. CONCLUSIONS: It was confirmed that the inner ear antigens come from different part of auditory system, which could cause cochlear or retrocochlear autoimmune disease.

Animals↗

Low-frequency sensitivity in a gerbilline rodent, Pachyuromys duprasi.

The contribution of the bulla to low-frequency hearing capability was studied in the gerbilline rodent Pachyuromys duprasi. In the frequency range of 0.6-3 kHz, the sound pressure behind the tympanic membrane is higher than the pressure in the meatus acusticus externus near the eardrum. Gradual augmentation of frequencies above 0.6 kHz gives rise to steadily increasing phase lag in the bulla relative to that in the meatus. Severing of the incudostapedial joint yields results indicating that the phase difference between meatus and bulla is caused by resonance properties of the bulla and resistance in the cochlea. Both destruction of the bulla and stiffening of the pars flaccida tympani lead to a sound pressure decrease in the frequency range around 2 kHz. This drop is accompanied by an amplitude decrease of the same magnitude in the cochlear microphonic potentials. These results support the hypothesis that the bulla functions like a Helmholtz resonator in the frequency range of 1-3 kHz, improving sound transduction to the cochlea. These experimental findings, in conjunction with theoretical considerations involving bulla volume, orifice area of the resonator, and resonance frequency of the bulla, suggest that the theoretically required area of the resonator's orifice is, in fact, of the same magnitude as the area of the pars flaccida tympani. The middle-ear system of P. duprasi thus consists of a resonating bulla in which the area of the pars flaccida tympani constitutes the resonator's opening towards the meatus and in which the pars tensa tympani functions as a pressure gradient receiver, due to phase differences caused by the resistance of the cochlea and by the resonance properties of the bulla. By these functional principles the peripheral auditory system of P. duprasi is capable of low-frequency perception despite the smallness of its structures. The middle ear in P. duprasi thus represents a prime example of a strategy: the dimensional constraints derived from a general bauplan for the peripheral auditory system have here been overcome.

Animals↗

Intrinsic oscillations in spike trains indicate non-renewal statistics due to convergence of inputs in dorsal cochlear nucleus neurons.

The occurrence of intrinsic oscillations (IOs) in a unit's discharge is reflected by a prominent peak in the power spectrum (i.e., Fourier transform of the autocorrelation function) of spike trains obtained from single-unit discharge, at a frequency independent of stimulus spectral characteristics. IOs have been reported by researchers in the dorsal cochlear nucleus (DCN) of both the cat and the Mongolian gerbil. It has been hypothesized that IOs are related to inter-spike interval (ISI) regularity (e.g., [Hear. Res. 58 (1992) 153]). This hypothesis is tested in this paper. Responses to multiple presentations of 50-300 ms duration tone bursts, at and near the unit's best frequency (BF) at 20-60 dB re threshold were recorded from DCN units of barbiturate-anesthetized (30 units), as well as decerebrate (53 units) Mongolian gerbils. IOs in the recordings were then compared with the IOs in simulations of spiking-neuron models. The models were selected because: (1) their ISI regularity characteristics follow those of experimental data and (2) their IO properties are completely determined by their ISI regularity. Such comparison reveals that Ghoshal's hypothesis fails for a fraction of the units. These results suggest a re-evaluation of the purported relationship between IOs, ISI regularity, and SAM response. Alternate hypotheses are proposed here using computational models that are based on convergence of multiple neural inputs onto the unit under study. These models produce non-renewal statistics that resemble those of the experimental data, as is evident from IO-based analysis.

Action Potentials↗

Analytic treatment of the compound action potential: estimating the summed post-stimulus time histogram and unit response.

The convolution of an equation representing a summed post-stimulus time histogram computed across auditory nerve fibers [P(t)] with an equation representing a single-unit wave form [U(t)], resulted in an analytic expression for the compound action potential (CAP). The solution was fit to CAPs recorded to low and high frequency stimuli at various signal levels. The correlation between the CAP and the analytic expression was generally greater than 0.90. At high levels the width of P(t) was broader for low frequency stimuli than for high frequency signals, but delays were comparable. This indicates that at high signal levels there is an overlap in the population of auditory nerve fibers contributing to the CAP for both low and high frequency stimuli but low frequencies include contributions from more apical regions. At low signal levels the width of P(t) decreased for most frequencies and delays increased. The frequency of oscillation of U(t) was largest for high frequency stimuli and decreased for low frequency stimuli. The decay of U(t) was largest at 8 kHz and smallest at 1 kHz. These results indicate that the hair cell or neural mechanisms involved in the generation of action potentials may differ along the cochlear partition.

Acoustic Stimulation↗

Electrical correlates of mechanical events in the cochlea.

In this paper the main emphasis is laid on presenting an up-to-date description of the relationships between stimulus-related cochlear potentials: cochlear microphonic (CM) and summating potential (SP) and the preceding mechanical events. To this end, CM and SP (both DIF and AVE SP) magnitude functions, obtained with the differential electrode technique, are shown from various turns of the guinea pig's cochlea as recorded at a constant stapes displacement. The similarity between these curves and corresponding basilar membrane displacement functions is considered. The influence upon CM recording of the distributed nature of the generators, as well as the presence of strong nonlinear effects is discussed.

Acoustic Stimulation↗

[Electrocochleography by extra- and transtympanic methods: the results in a group of normal subjects].

Electrocochleography (ECoG) is an electrophysiologic approach to the study of hearing. In ECoG, electrical activity that originates within the cochlea or the auditory nerve is recorded. ECoG represents an evoked or stimulus dependent measure. The electrical potentials which can be analyzed in ECoG are: the cochlear microphonic potential (CM), the summating potential (SP) and the acoustic nerve potential (AP). Two major types of electrocochleography electrodes can be used, transtympanic and extratympanic. Transtympanic ECoG is performed by inserting a long needle electrode, placed through the tympanic membrane onto the promontory. Extratympanic ECoG is recorded by using electrodes placed within the external meatus near the tympanic membrane. At the ENT Department of the University of Parma, ECoG was performed in 10 normal hearing subjects (4 males and 6 females. Their ages ranged from 21 to 29 years (mean 26 years). All subjects underwent ECoG recording simultaneously with extratympanic and transtympanic technique.

Adult↗

Ototoxicity of kanamycin in developing guinea pigs. An electrophysiological study.

Pregnant guinea pigs were treated with Kanamycin at three different stages of gestation (dating by method of post-partum ovulation). Twenty-nine newborn guinea pigs were tested electrophysiologically by recording the cochlear microphonic potential and the compound action potential from the round window in response to clicks and filtered clicks at 8,000 Hz. Six of the test animals showed the same electrophysiological changes as those found in adult mammals after Kanamycin intoxication. The results suggest a relationship between the ototoxicity of Kanamycin and the onset of auditory function. Cochlear potential and compound action potential were mostly affected when intoxication was performed during the last 15 days of gestation. This study confirms the results previously published by Uziel 1979.

Action Potentials↗