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PubMed1993

Electrical tinnitus suppression: frequency dependence of effects.

Electrical stimulation through a round window electrode has been evaluated in 9 patients with unilateral deafness and severe tinnitus. Three subjects were permanently implanted with positive long lasting results. Analysis of the threshold of sound perception, tinnitus suppression and auditory discomfort levels as a function of current frequency revealed the advantage of low frequency stimulation. In 2 patients the loudness of electrically evoked sound perception was balanced against tones in the hearing ear. Our results can be interpreted as indicating that processes other than auditory masking are responsible for electrical tinnitus suppression.

Acoustic Stimulation↗
PubMed1987

The permeability of the round window membrane during otitis media.

Studies of the permeability of the round window membrane (RWM) during otitis media are important because toxins and cellular components that occur in otitis media as well as pharmacologic agents used in treating the disease have the potential to cross the RWM and pass into the inner ear. Twenty-five cats were evaluated electron microscopically as to the passage of a tracer, horseradish peroxidase, through normal RWMs and RWMs three days, one week, and two weeks following eustachian tube obstruction. Passage at three days following obstruction was similar to passage through the normal RWM. Following one to two weeks of obstruction, the permeability of the membrane was drastically reduced. The reduction in permeability was probably due to the presence of residual effusion overlying the membrane, the presence of granulation tissue within the niche, and a thickening of the RWM.

Animals↗
PubMed2003

Role of mannitol in reducing postischemic changes in distortion-product otoacoustic emissions (DPOAEs): a rabbit model.

OBJECTIVES: The aim of this study was to observe the effects of mannitol, administered topically at the round window (RW), on cochlear blood flow (CBF) and distortion-product otoacoustic emission (DPOAE) after repeated episodes of cochlear ischemia. METHODS: Ten young rabbits were used for this study. Reversible ischemic episodes within the cochlea were induced by directly compressing the internal auditory artery (IAA). CBF was measured using a laser-Doppler (LD) probe positioned at the RW niche. DPOAEs were measured at 4, 8, and 12 kHz geometric mean frequency (GMF) using 60 dB sound pressure level (SPL) primary tone stimuli. In five test ears, mannitol was administered topically at the RW for 30 minutes before the IAA compressions. In five control ears, the IAA compressions were undertaken without application of RW medication. Each ear underwent three 5 minute IAA compressions with a 60 minute rest period between compressions. RESULTS: In the control animals, it was observed that a progressive reduction in DPOAE level followed each successive IAA compression at all three test frequencies. The reduction in DPOAE amplitudes was consistently greater at the higher test frequencies. In the test rabbits, the RW administration of mannitol resulted in significantly less reduction in DPOAE level measures after repeated IAA compressions. For example, 30 minutes after reperfusion at 12 kHz GMF, DPOAE levels in the control ears were reduced by 1.5, 6.0, and 16 dB, compared with 1.5, 4.0, and 6.0 dB in the mannitol test ears. CONCLUSIONS: Mannitol appears to exert a protective effect on cochlear function after periods of ischemia. The RW appears to be an efficacious route for topical administration of mannitol into the inner ear.

Acoustic Stimulation↗
PubMed1989

Correlative changes of auditory nerve and microphonic potentials throughout sleep.

Gross cochlear potentials in response to alternating clicks and pure tone bursts were recorded in guinea-pigs with chronically implanted electrodes in the round window during sleep and the awake state. A significant increase in both averaged potentials, the compound auditory nerve action potential (cAP) and cochlear microphonics (CM) occurred in slow wave sleep (SWS) with a subsequent diminution in paradoxical sleep (PS) periods. The cAP, CM, amplitude and area averages were similar during quiet wakefulness and in PS. Moreover, as an episode of PS progressed, the recorded potentials continued to decrease. On the other hand, increased averaged values were again observed during a subsequent episode of SWS. An involvement of the efferent olivo-cochlear bundle is postulated, first, because it is the only known pathway connecting the CNS and the auditory periphery and, second, because several key pre-receptor variables (middle ear muscles and ossicles and sound-source ear relation) were either abolished or altered dramatically.

Acoustic Stimulation↗
PubMed2004

Round window pH manipulation alters the ototoxicity of systemic cisplatin.

The effect of manipulation of pH on the ototoxicity of systemic cisplatin was studied in Wistar rats. After control auditory brainstem responses (ABR) were performed, the auditory bullae were opened and acidic (pH 6.0), neutral (pH 7.4) or basic (pH 9.0) phosphate-buffered saline (PBS) was applied to fill the round window niche (RWN). After 30 min, 13 mg/kg cisplatin solution or saline was administered intraperitoneally. After 3 days, follow-up ABRs were performed and cochleae were processed for morphological analysis. Animals that received basic PBS on the RWN and cisplatin intraperitoneally had significantly smaller ABR threshold shifts compared to rats pretreated with neutral pH buffer (P<0.05). Animals that received acidic PBS on the RWN and systemic cisplatin showed significantly greater ABR threshold shifts compared to those pretreated with neutral pH buffer (P<0.05). No significant threshold changes were observed in animals that received buffer of any pH on the RWN, followed by saline intraperitoneally. Semiquantitative analysis of hair cell survival confirmed a protective effect by basic PBS against cisplatin and a synergistic effect by acidic PBS on cisplatin ototoxicity (P<0.05). It appears that changes in cochlear pH can modulate the ototoxic effects of systemically applied cisplatin.

Animals↗
PubMed1976

[Otitis media and cochlea. Morphological and biochemical studies in guinea pigs (author's transl)].

The paper deals with: 1. the protein concentration in the perilymph (PL), the serum and the cerebrospinal fluid (CSF), 2. the protein pattern in the PL and 3. histological findings in the middle and inner ear in unilaterally ear-infected guinea pigs. The studies were performed 6 h to 21 days post infectionem (Fig. 1). The pathological changes in the middle ear, which, in most cases, were limited to the infected ear, were initially evaluated under the operating microscope and divided into 4 stages. The analytical and histological results were presented as functions of these stages. As the inflammation intensity increased, the protein concentration in the PL of the infected ears increased to a level exceeding that of the normal value more than ten times (Fig. 2). However, in the serum and in the CSF this concentration remained unchanged. Likewise, no significant protein increase in the PL of the contralateral ears was detectable in most cases. As the inflammation intensity increased, the number of the precipitation lines detectable immunoelectrophoretically increased in the PL of the infected ears (Fig. 3). An increase in the alpha1- and gamma-globulins and a decrease in Albumin was found by electrophoresis on cellulose acetate strips (Tab. 3). The histological findings correlated with initially established inflammatory stages of the middle ear mucous membrane (Tab. 4). As the inflammation intensity increased, the round window, too, was changed pathologically, so that in some cases of purulent otitis media middle ear secretion could enter the cochlea. The protein increase in the PL immediately after the infection is probably due to an increase in the blood vessel permeability in the inner ear.

Animals↗
PubMed1993

Round window membrane in serous and purulent otitis media. Structural study in the rat.

The rat was used as an animal model to reveal structural alterations in the round window membrane (RWM) during serous otitis media (SOM) and purulent otitis media (POM) over a 6-week period. Comparison of POM animals and control animals showed that the RWM in the former became almost six times as thick as that in controls, whereas that of SOM animals was twice as thick. The structural changes in the RWM in POM animals were confined mainly to the epithelium facing the middle ear cavity and the subepithelial space, which was invaded by inflammatory cells and exhibited dilated vessels. The normal flat epithelium was transformed via cuboidal cells to a cylindric epithelium containing both ciliated and goblet cells. In SOM animals, light microscopy revealed only minor changes in the RWM structure. Ultrastructurally, however, the connective tissue layer exhibited dense aggregations of collagen, increased numbers of fibroblasts, and, in one case, elastic fibers. This last phenomenon was not observed in either POM ears or normal ears. The study showed that various inflammatory conditions of the middle ear, both noninfectious (SOM) and infectious (POM), can cause different structural alterations of the RWM. These structural changes may influence passage through the RWM differently.

Animals↗
PubMed1997

Electrical and physiological changes during short-term and chronic electrical stimulation of the normal cochlea.

In the electrical stimulation (ES) of auditory pathways, the type of stimulus and the electrode/tissue interface are critical parameters for the safety and efficacy of the protocol. In this study the influence of alternate pulses, applied between round window and vertex electrodes in chronically implanted guinea pigs, and maintained during 1 and 25 daily periods of 2 h (short-term and long-term experiments, respectively), was investigated. ES consisted of monophasic current pulses of +/- 70 microA and 300 (micro)s in duration at a rate of 167/s, with alternate polarity. Compound Action Potential (CAP) audiograms, amplitudes and latencies of click-evoked CAPs, amplitudes and latencies of electrically-evoked auditory responses (EARs), and electrode impedances, were measured periodically outside or during the ES periods. Short-term ES induced no change in CAP thresholds, amplitude and latency in response to clicks at 80 dB above normal threshold, but induced a slight latency increase and amplitude decrease of the EAR, correlated with an exponential decay of the electrode impedance. On a long-term basis, CAP audiograms and latencies did not change significantly, whereas CAP amplitudes and electrode impedances increased, in correlation with each other. In control guinea pigs receiving no ES, the same CAP amplitude and impedance changes were observed over the same long-term period. The EAR and CAP changes can be explained by a variation of the electrical impedance of the electrode/tissue interface. This is possibly due to a change in electrolytes around the electrode under the influence of the ES for the short-term variation, and to an electrode encapsulation by fibrous tissue independent of the ES for the long-term change. In itself, and under the conditions of this experiment, the ES demonstrated no adverse effects on the auditory function and can be safely used for inner-ear exploration.

Acoustic Impedance Tests↗
PubMed1981

Animal models of tinnitus.

There are few physiological data available on the origin and nature of tinnitus. It is not even known whether tinnitus associated with cochlear pathology is a manifestation of increased or decreased activity in the cochlear nerve. In previous investigations of cochlear pathology, the spontaneous neural activity has generally been found to be depressed. In the present experiments, an animal model has been established by the administration of sodium salicylate in doses producing blood concentrations that evoke tinnitus in humans. Under these conditions, changes occur in cochlear nerve-fibre thresholds and tuning, similar to those obtained in other types of cochlear pathology. However, under salicylate, the distribution of spontaneous discharge shifts significantly to higher rates than normal. These changes are accompanied in some, but not all, fibres by changes in the temporal patterns of discharge suggestive of excitation. In the second animal model studied, a normal guinea-pig that had a naturally occurring continuous tonal emission, analogous to that recently recorded in human "physiological" tinnitus, was investigated in detail. The emitted signal was recorded in the ear-canal acoustic pressure and in the round-window potential. Several lines of evidence point to the signal as being cochlear in origin, including: its resistance to muscular paralysis and section of the stapedius muscle; the effects of changes in middle-ear pressure; its reversible elimination by hypoxia; and its suppression by tones of higher frequency.

Acoustic Stimulation↗
PubMed1992

Electrocochleography in the diagnosis of perilymphatic fistula: intraoperative observations and assessment of a new diagnostic office procedure.

The intraoperative electrocochleogram (ECochG) was investigated during stapedectomy surgery and during cochleostomy surgery. This provided the justification for obtaining recordings with the oval window (OW) or round window (RW) intact and then when there was a definite fistula. It was noteworthy that no ECochG changes occurred on merely opening the OW or RW, but that marked changes occurred on removing perilymph, even by gentle suction. On raising the intrathoracic pressure and replacing the perilymph, the ECochG potentials usually recovered. Based on these intraoperative observations, an office procedure was designed. The subject was asked to raise the intrathoracic pressure on several occasions and changes in the amplitude of the ECochG potential were noted. An increase of over 15 percent in the action potential (AP), with or without a decrease in the negative summating potential (SP) during the period of raised intrathoracic pressure, was used as the diagnostic criteria for a perilymphatic fistula. A decrease in the AP with or without an increase in the negative SP immediately on relaxing after a period of raised intrathoracic pressure was also treated as a positive diagnostic criterion. Seventy-one normal ears were investigated and a positive result was recorded in two ears (false positive rate: 2.8%). Two hundred and six ears, strongly suspected as having a perilymph leak on the basis of the clinical history and vestibular signs have been investigated over the past 4 years. Ninety positive diagnoses have been reached and 46 of these ears have been surgically explored.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed2006

Response of cochlear blood flow to prostaglandin E1 applied topically to the round window.

CONCLUSIONS: The increase in cochlear blood flow (CBF) after administration of prostaglandin E1 (PGE1) to the round window depends on increased blood flow through the anterior inferior cerebellar artery (AICA). OBJECTIVES: To evaluate the response of CBF to PGE1 applied topically to the round window, and to investigate the origin of blood flow changes after this topical application. MATERIAL AND METHODS: The response of CBF to topically applied PGE1 was measured by placing the tip of a laser Doppler probe on the bony wall of the basal turn of the cochlea after the middle ear mucosa over the cochlea had been removed in guinea pigs and rats. In rats, the CBF response to PGE1 administration was investigated after occlusion of the AICA or stapedial artery. RESULTS: CBF increased following PGE1 administration in both guinea pigs and rats. In rats, CBF increased from 100% to 132%+/-10% (mean+/-SD) after the topical application of 0.5 microl of a 0.014% PGE1 solution. CBF decreased after occlusion of the AICA or stapedial artery but did not increase after PGE1 administration during occlusion of the AICA. The CBF response to PGE1 administration was similar before and after occlusion of the stapedial artery.

Administration, Topical↗
PubMedDate not supplied

Experimental perilymphatic fistula.

Perilymphatic fistula was produced in guinea pigs by injecting artificial perilymph into the subarachnoid space of the posterior fossa. Rupture of the round window was confirmed by direct observation of the round window membrane under a surgical microscope during the injection. The animals were either vitally fixed or kept alive for one to three months before fixation. Conventional celloidin embedding method was used for serial sectioning. In immediate observation, nine cochleas showed hydrops, seven showed collapse, and 20 of 36 cochleas showed no change. Changes in the vestibular apparatus varied, with collapse of the membranous vestibular labyrinth as the main change. Delayed observation revealed 16 normal cochleas and four collapses and no hydrops out of 20 ears. Of these 20, nine ears showed normal vestibular apparatus, nine collapse, and two saccule hydrops. Loss of the outer hair cells was observed in five of 20 cochleas. Marked compression of the organ of Corti was seen in both immediate and delayed observations.

Animals↗
PubMed2000

Round window membrane permeability to transforming growth factor-alpha: an in vitro study.

OBJECTIVE: Recent studies have identified the capacity of transforming growth factor-alpha (TGF-alpha) to stimulate mammalian labyrinthine hair cell regeneration after acute ototoxic damage. Augmenting hair cell regeneration with such growth factors may have a role in potentiation of recovery of cochlear function after hair cell injury. Transtympanic application of aqueous solutions to the round window membrane (RWM) has proved successful as a drug delivery route. The purpose of this study was to test the permeability of the mammalian RWM to TGF-alpha in an inexpensive and reliable in vitro model. METHODS: Guinea pig RWM niches were harvested and transferred to a 2-chamber apparatus, and TGF-alpha was applied to the middle-ear side of the chamber. ELISAs of TGF-alpha were measured at intervals during a 96-hour period. RESULTS: Aliquots taken during a 96-hour interval demonstrated passage of TGF-alpha in concentrations sufficient to stimulate hair cell regrowth. CONCLUSIONS: The apparatus allows study of RWM permeability to other substances and provides a basic model for study of RWM physiology. TGF-alpha is able to pass through a mammalian RWM.

Animals↗
PubMed2003

Contamination of perilymph sampled from the basal cochlear turn with cerebrospinal fluid.

Our understanding of the perilymph kinetics of drugs depends largely on data obtained by the analysis of perilymph samples. Although a number of studies have demonstrated qualitatively that perilymph samples may be contaminated by cerebrospinal fluid (CSF), and some investigations adopt specific methods to minimize CSF contamination of their samples, many other studies fail to consider the influence of this potential artifact on their measurements. In the present study we have attempted to quantify the degree of CSF contamination of perilymph samples taken from the basal turn of the guinea pig cochlea using the ionic marker trimethylphenylammonium (TMPA). TMPA solution was irrigated across the round window membrane while a TMPA-selective electrode sealed into the perilymphatic space continuously monitored perilymph TMPA concentration. After a period of TMPA loading, a perilymph sample was aspirated and its TMPA content determined. Differences between the sample concentration and the measured TMPA time course during perilymph loading and sampling were analyzed using a finite element computer model for simulation of solute movements in the inner ear fluids. The experimental results were consistent with the aspirated fluid sample from the cochlea being replaced by CSF drawn into the perilymphatic space through the cochlear aqueduct. The dependence of perilymph sample purity on the location of sampling and on the volume withdrawn was quantified. These relationships are of value in the design and interpretation of experiments that utilize perilymph sampling.

Animals↗
PubMed1988

Independent fluctuations of the round-window summating potential and compound action potential following the surgical induction of endolymphatic hydrops in the guinea pig.

The diagnosis of Menière's disease is classically based on the triad of symptoms including fluctuating hearing loss, tinnitus and vertigo. Modifications to the electrocochleographic response have been searched as a possible help in the diagnosis. Various authors have reported a tendency for an increased ratio of the summating potential (SP) to action potential (AP) which is generally thought to be due to an enhanced SP. However, the large variability between patients has precluded any clear-cut conclusion. This dispersion of data might represent real individual differences or might be attributed to unavoidable technical variations, such as electrode placement and/or precise control of stimulus levels. As an attempt to answer this issue, we employed an animal model of experimental hydrops in which these difficulties can be overcome by chronic implantation of round-window electrodes and carefully controlling the stimulus level. In the present study, the SP and AP were monitored over several months for different frequencies and different intensities. In the early period of fluctuating thresholds at low and mid frequencies, AP amplitude varied in loose correspondence with the fluctuating audiogram. The SP amplitude also varied apparently not associated with AP or threshold changes and no consistent increase in SP was observed. At a later stage when all thresholds were elevated both SP and AP diminished. In normal ears increases in the stimulus intensity induce an augmentation of SP/AP. In hydropic ears, at the period of fluctuating thresholds, the SP/AP growth curve was at first similar to that of controls but later became very variable for different animals, but in general much larger than normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1990

Outer hair cells as potential targets of inflammatory mediators.

Inner ear sequelae with temporary or permanent sensorineural hearing loss can result from inflammatory processes in the middle ear. Loss of outer hair cells in the base of the cochlea has been noted in otitis media, but it is not known how this damage occurs. Evidence supports the permeability of the round window membrane to substances mediating inflammation in the middle ear, and the presence of white blood cells has been reported in the perilymph. In the present study, the potential cytotoxic effects of two representative inflammatory mediators, endotoxin and free radicals, have been evaluated by use of short-term culture of isolated outer hair cells from the guinea pig cochlea model. Incubation with endotoxins from two gram-negative pathogens increased the rate of hair cell death fourfold to sixfold. Free radicals (generated by exposure of cells to UV light or by excitation of intracellular fluorescent dyes) produced morphologic damage to hair cells within 60 seconds. These latter effects were delayed by addition of free-radical scavengers. It is concluded that inflammatory mediators are cytotoxic to hair cells and therefore are potentially ototoxic if permeating the round window membrane.

Animals↗