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Morphologic changes in round window membrane after topical hydrocortisone and dexamethasone treatment.

HYPOTHESIS: Are all glucocorticoids supposed to have the same effect on the round window membrane? BACKGROUND: Interest in glucocorticoids for topical treatment of inner ear diseases is increasing. The safety of such treatment should therefore be an important consideration before clinical use. METHODS: In this study the authors investigated the morphology of the round window membrane after topical instillation of dexamethasone or hydrocortisone into the middle ear. Twenty Sprague-Dawley rats were used. Five rats received 5 doses, and five rats 10 doses, of 1 microg (20 microl) dexamethasone in the right ear, and five others were given 5 doses, and five rats 10 doses, of 2% (20 microl) hydrocortisone solution, also in the right ear. Membrane morphology was studied in both light microscopy and transmission electron microscopy. The thickness of exposed membranes was measured and compared with that of control membranes. RESULTS: Thickening and microscopically signs of inflammation were observed in hydrocortisone-exposed membranes but not in dexamethasone-exposed membranes, which did not differ morphologically from those in control ears. CONCLUSION: Although hydrocortisone has anti-inflammatory properties, it seems to provoke inflammation in the round window membrane after topical instillation. Dexamethasone had no such effects, however.

Administration, Topical↗

[Blockage of cochlear aqueduct for examination of perilymph (guinea pig) (author's transl)].

To prevent the perilymph (guinea pig) from contamination with CSF during the sampling the aqueductus cochleae (AC) was blocked by injection of tissue adhesive into the meningeal aperture. The control of an exact blockage of AC was carriedout by examination of perilymph-outflow after opening the cochlea (injection of fluorescein-Na into the CSF-space), analysis of perilymph-protein-concentration, macroscopic and microscopic examination of the temporal bones. In all cochleae we have found the same morphological structures, notwithstanding whether the AC was blocked (for a time from 30 min to 7 weeks) or not: The cochlear aqueduct is filled with a mesh of mesenchymal tissue, which grows more dense towards the cochlear aperture andcontinues into the round window membrane. From scala tympani the AC is always limited by one layer of cells forming a sort of membrane (under light microscope). It seems possible that CSF moves in the inner of the round window membrane between AC and subepithelian space of middle ear mucosa, whereas perilymph of scala tympani is not in direct contact with the flow of CSF. The scala tympanic side of the round window membrane may be a big area for diffusion and there also may be an exchange between CSF and perilymph. The outflow of CSF into the cochlea after experimental opening of the cochlea is an artifact, caused by damage of pressure equilibration between CSF-space and cochlea. 30 min and 5--7 weeks after blockage no morphologicaland electrophysiological alterations from those of the control ears were to be seen. The protein concentration, however, increased significantly 5--7 weeks after blockage from normally about 200 mg/100 ml toalmost the double especially in the scala tympani (see Table 1).

Action Potentials↗

Infiltration of the tensor tympani and stapedius muscles in otitis media. An experimental study in the cat.

A longitudinal sequential study of otitis media was done in an experimental animal (cat) using eustachian tube obstruction. Fifty animals were used. Cellular infiltration of the tensor tympani and stapedius muscles was studied in a continuum from day 1 to 6 months after inducing otitis media. We observed that there is infiltration of the connective tissue of both muscles in otitis media, and that the cellular changes follow the same pattern as that seen in the mucoperiostium and the round window of the middle ear, although to a lesser degree. In this first report of sequential changes in middle ear muscles in otitis media, clinical implications of these findings are discussed.

Animals↗

Structural effects of short term and chronic extracochlear electrical stimulation on the guinea pig spiral organ.

To assess the effects of extracochlear electrical stimulation on cochlear structure, guinea pigs were implanted and stimulated with single middle ear electrodes either at round window or promontory sites, and their cochleae examined by transmission electron microscopy. Implanted but unstimulated, or unimplanted control animals were examined in the same way. Alternating current stimulation at the promontory for 2 h at 150 Hz, 500 microA, caused outer hair cell efferent endings to become dense and vacuolated, but no hair cells were damaged. With direct current stimulation at 500 microA for 2 h the basal regions of the stimulated cochlea were badly damaged and many outer hair cells lysed. Long term (up to 1200 h) round window stimulation at 100 or 141 Hz, 15-91 microA rms, did not cause cell death or inner hair cell damage, but basal outer hair cells and their efferent endings were badly affected in both ipsilateral and contralateral cochleae. The compound action potential of the auditory evoked response to broad band click stimuli was not altered by chronic electrical stimulation. It is concluded that chronic stimulation with the parameters used does not threaten cochlear survival, and it is proposed that the bilateral structural changes induced by chronic stimulation are caused by excessive activation of the cochlear efferent pathways.

Animals↗

Pattern of hearing loss in a rat model of cochlear implantation trauma.

HYPOTHESIS: Trauma caused by cochlear implant electrode insertion is attributable to the combination of direct physical trauma and the delayed cell death of oxidative stress-injured auditory sensory cells. BACKGROUND: Histologic evaluation of cochlear implant electrode trauma has demonstrated that the extent of sensory cell losses is proportional to the degree of injury. However, the impact of delayed oxidative stress within injured cochlear tissues and the progressive loss of injured hair cells by way of apoptosis are at present unknown. METHODS: Laboratory rats were evaluated for hearing acuity before and after electrode insertion, before and after round window membrane incision only. Hearing was measured before trauma or incision and over the next 7 days. Objective measurements of hearing function were distortion products of otoacoustic emissions (DPOAEs) in the frequency range of 2 to 32 kHz and tone-burst (i.e., 4-32 kHz) evoked auditory brain stem responses (ABRs). RESULTS: For the experimental cochleae, there were progressive increases in ABR thresholds and decreases in ABR amplitudes. The amplitude of the DPOAEs in the experimental cochleae also showed progressive decreases. For the contralateral control and round window membrane surgical control ears, there were no significant changes in either DPOAE or ABR thresholds. CONCLUSION: These results document a progressive loss of hearing acuity postimplantation and strongly suggest that electrode insertion trauma generated oxidative stress within injured cochlear tissues.

Animals↗

Hemodynamic changes in skin microcirculation induced by vibration stress in the conscious rabbit.

Cutaneous microcirculatory responses to vibration stress were observed by microphotoelectric plethysmography in a transparent round window installed in the ears of conscious rabbits. Vertical vibrations at frequencies ranging from 8 to 250 Hz were applied to the abdomen of the rabbits for 5 min. The vibrations produced an increase in heart rate and the index of discomfort, and a decrease in blood flow in the skin microcirculation. The maximum response was observed at 63 Hz. Rhythmic fluctuations in microcirculation were associated with two components: component A had a small amplitude and high frequency, and component B had a large amplitude and low frequency. Vibration exposure led to a large increase in component B and a smaller increase in component A. During vibration exposure, component A was suppressed by treatment with diltiazem, a calcium channel blocker, and was not affected by bunazosin, an alpha-1 adrenoceptor antagonist. The opposite changes were observed for component B. This indicates that components A and B of the rhythmic fluctuations are regulated by myogenic and neurogenic activities, respectively. Thus, the hemodynamic changes of skin microcirculation induced by vibration may actually be due to a neurogenic factor, especially sympathetic nerve activity. The responses appear to depend on the frequency of the vibrations.

Animals↗

The effects of kanamycin injection into the fetal lamb cochlea.

Mammalian auditory hair cells have minimal capacity for repair or regeneration after a variety of insults, including acoustic trauma and aminoglycoside exposure. Although fetal tissues have a greater potential for repair and regeneration than adult tissues, there have been no reported studies on fetal hair cell response to injury in mammals. The purpose of this research was to investigate the effects of local application of kanamycin on fetal lamb cochlear hair cells. Eleven fetal lambs in the early third trimester underwent kanamycin injection through the left round-window membrane. The right ear served as a control. Click-evoked compound action potentials (CAPs) were serially recorded in 8 fetuses. CAPs were observed in all control ears. None of the 8 kanamycin-injected ears had measurable CAPs on postoperative day 1. One kanamycin-injected ear demonstrated definite CAPs, beginning on postoperative day 6. Hair cells were found to be intact in 6 of 9 kanamycin-treated ears. Hair cells were missing only in animals that went into premature labor. The presence of intact hair cells despite the loss of measurable CAPs in kanamycin-perfused lamb cochleae was striking. This finding may indicate that the fetal auditory epithelium is relatively resistant to aminoglycoside injury or may be capable of prompt repair or regeneration. Further studies on the effects of aminoglycoside injury in the fetal cochleae seem to be warranted.

Animals↗

Recovery of hearing following cisplatin ototoxicity in the guinea pig.

BACKGROUND: To report a spontaneous recovery of hearing, following cisplatin ototoxicity in the guinea pig. The findings are related to the animal and human literature on recovery from hearing loss following cisplatin ototoxicity. MATERIALS AND METHODS: Hearing was measured from compound action potentials (CAP) evoked by acoustic tones, which were monitored daily from an electrode implanted onto the round window of the inner ear. Cisplatin was administered at 2 mg/kg/day intraperitoneally until a hearing loss occurred. RESULTS: A hearing loss occurred suddenly across the frequency range and recovered over the period 2-14 days after treatment. The endocochlear potential was significantly lower than normal before hearing recovery and normal following recovery. CONCLUSION: These findings suggest a pivotal role for the endocochlear potential in the hearing loss from cisplatin ototoxicity and its recovery, and a plausible mechanism for the hearing recovery sometimes reported in patients following cisplatin ototoxicity.

Animals↗

[Effects of extrastimulation on morphofunctional state of cochlear stria vascularis].

An electron-microscopic study of the response of cochlear stria vascularis (CSV) cells to an electric impact of physiotherapeutic parameters was made in 26 guinea-pigs. Twelve guinea-pigs (group 1) have undergone 9 sessions of bilateral endaural electrostimulation with square bipolar impulses (4 ms, 0.1-0.4 mA, 50 Hz, 20 min). Fourteen guinea-pigs of group 2 have undergone a 12-18-day course of intramuscular ototoxic antibiotic canamycin in a dose 200-400 mg/day followed by the above electrostimulation. Nine anesthesized guinea-pigs of group 3 were inserted an electrode into the niche of the round window of the right ear. After a 10-day course of canamycin (200 mg/day) they were exposed to electrostimulation (8 sessions) with impulsed alternative current (100 Hz, 1 ms, 0.08 mA, 30 min). Five guinea-pigs served control. Morphofunctional state of CSV was assessed at electronograms by analyzing cell ultrastructure and counting the number of secretory vacuoles in the apical region of marginal cell cytoplasm. In group 1 there was intensification of biosynthetic processes in all CSV cells and a significant (p<0.01) increase of vacuole number in the marginal cells (53.9+/-3.8) vs normal value (33.9+/-1.5). In group 2 ultrastructure of all CSV cells was less affected and secretory activity was almost normal (31.4+/-2.9). CSV cell condition was similar to ultrastructure of the cells in group 2. The number of vacuoles in CSV marginal cells of the right (28.9+/-1.98) and left (29.1+/-5.4) cochleas was similar. Thus, electrostimulation activates biosynthetic processes in CSV structures and enhances secretory activity of marginal cells.

Animals↗

Electrocochleography in profoundly deaf children: comparison of promontory and round window techniques.

It is important to be able to accurately assess residual cochlear function in profoundly deaf children. Profound hearing loss in children requires special consideration, because the choice between a cochlear implant and a hearing aid depends on accurate estimation of the residual hearing. Previous reports confirm that promontory (needle) electrocochleography (ECochG) is useful for evaluation of residual hearing in severely deaf children, but there were some limitations in assessing the lower audiometric frequencies and for assessing profound hearing loss. It is argued that accurate placement of a round window electrode (RW ECochG) provides better recordings. Round window ECochG testing is performed under general anesthesia in young children and gives an opportunity for inspection of the middle ear using an endoscope. This report describes a special "golf club" electrode that can be placed under direct vision into the round window niche, minimizing the risks of damaging an abnormal round window while providing the optimum extracochlear recordings. Round window ECochG gives better responses, especially in lower audiometric frequencies, than conventional promontory ECochG. In the Sydney children's cochlear implant program, RW ECochG has become an essential preoperative test.

Audiometry, Evoked Response↗

Round window membrane permeability. An in vitro model.

The round window membrane is regarded to be the main route for passage of potentially ototoxic substances from the middle ear cavity into the inner ear. This may be of clinical importance in acute otitis media and chronic otitis media, where sensorineural hearing impairment sometimes develops. The accuracy and reliability of an in vitro round window membrane permeability model was studied. The round window membrane of the mongolian gerbil was resected, together with its bony niche. The preparation was mounted between two glass chambers representing the middle ear and the inner ear. Passage through the round window membrane did not occur within 3 h for low density lipoprotein with a molecular weight of 2,300 kD. Only minute amounts of highly density lipoprotein, of molecular weight 115-350 kD, passed the round window membrane. The passage rate of horseradish peroxidase, which has previously been shown to pass the round window membrane in vivo, was estimated. The design of the present model is considered to make feasible controlled permeability studies on the round window membrane. Passage rates for different substances through the round window membrane can be calculated under controlled conditions by using this type of in vitro model.

Animals↗

[Feasibility of inner ear gene transfer after middle ear administration of an adenovirus vector].

BACKGROUND: Several groups demonstrated in animal experiments that gene transfer is a feasible tool for inner ear intervention. Various approaches for inoculation of vectors have been successfully used for inner ear gene therapy. One possible way to reduce the risk of hearing loss following the opening of the cochlea for application of the vector into the perilymphatic space is to deliver vectors through the round window. This study was designed to determine whether middle ear application of an adenoviral vector is a feasible approach to inoculate vectors and lead to transduction of cells in the inner ear. METHODS: A unilateral middle ear application of an adenoviral vector was performed in 4 guinea pigs directly on the round window membrane (RWM) and in 4 additional animals by placing a cotton patch soaked with the vector solution on the RWM. The expression of a reporter gene (lacZ) was used to localize vector-transduced cells. RESULTS: Only one out of 8 animals showed cochlear expression of the reporter gene, whereas all 8 animals showed strong lacZ expression in the middle ear mucosa, in the RWM and in the mucosa surrounding the stapes. CONCLUSION: Our results indicate that the RWM presents a close barrier, almost completely preventing the adenovirus to diffuse into the perilymphatic space. Therefore middle ear application of an adenoviral vector cannot be used to induce inner ear gene transfer. However, middle ear application of a viral vector may be useful for developing treatment for diseases of the middle ear mucosa.

Adenoviruses, Human↗

Electrical stimulation of the ear: clinical applications.

Electrical stimulation of the ear in humans was performed with an extracochlear electrode on the round window. With positive currents, suppression of tinnitus could be induced. With negative currents, auditory sensations were evoked. Since electrical stimulation with DC currents may be hazardous in the long term, it cannot yet be proposed for the suppression of tinnitus. However, electrically evoked hearing sensations with AC currents seem to be of definite interest for some totally deaf patients.

Deafness↗

ECoG and perilymphatic fistulae: an experimental study in the guinea pig.

Perilymph fistulae present a diagnostic dilemma to the clinician. As yet, there is no readily available, widely accepted diagnostic test. Electrocochleography (ECoG), with the advent of extratympanic recording techniques, has become a clinically applicable probe of cochlear function. Clinical ECoG was used to study guinea pigs (n = 35) both before and after surgical fistulization (n = 18) or fistulization and repair (n = 17) of the round window membrane. The animals were killed, and histopathologic examination of the temporal bones was carried out 0, 1, 3, 4, 7, 10, 14, 21, and 28 days after surgery. Of the 33 animals that survived surgery, 30 demonstrated ECoG wave-forms. No significant difference between the preoperative and postoperative wave-forms could be detected. Histopathologic study showed rapid healing of the fistulae, with no evidence of hydrops. Although there appeared to be a relatively selective loss of the outer hair cells of the cochlear basal turn, autolysis precluded detailed analysis. ECoG, as performed clinically, does not appear to detect the presence, spontaneous healing, or repair of a round window membrane fistula in the guinea pig.

Animals↗

The round window electromagnetic implantable hearing aid approach.

The round window electromagnetic implantable hearing aid (RWEM) approach uses a magnet surgically implanted onto the round window membrane of the cochlea to impart vibrational energy to the inner ear when driven by a nearby electromagnetic coil. In this article, experimental methods used in animal ABR studies are described for this approach and evidence for the viability of this technique is demonstrated by the similarity of ABR waveforms obtained using RWEM and acoustically-evoked stimuli.

Animals↗

Congenital perilymphatic fistula: computed tomography appearance of middle ear and inner ear anomalies.

Congenital perilymphatic fistula is an abnormal communication between the inner ear and middle ear. Inner ear anomalies have been described on computed tomography scans. Middle ear anomalies have been found at surgery; the most frequent are anomalies of the stapes and round window. This retrospective study describes the appearance of the inner and middle ear on computed tomography scans, and of the middle ear at surgery, in 10 patients (15 ears) in whom perilymphatic fistula was found at surgery. Twelve of 15 stapes were abnormal at surgery; 4 of these 12 (33%) could be seen on computed tomography scans. Two stapes normal at surgery were normal on computed tomography. Three round windows were abnormal at surgery; none of these was seen on computed tomography scans. There were also four dysplastic cochleas, four dysplastic vestibules, and three dilated vestibular aqueducts. Computed tomography scans identified an abnormal inner ear, middle ear, or both in 8 (53%) of the 15 ears with perilymphatic fistula. An inner ear or middle ear anomaly on computed tomography may heighten clinical suspicion of congenital perilymphatic fistula.

Adolescent↗

A self-mixing laser-diode interferometer for measuring basilar membrane vibrations without opening the cochlea.

A laser-diode forms the basis of a displacement sensitive homodyne interferometer suitable for measurements from poorly reflective surfaces. The compact and cost-effective interferometer utilizes the self-mixing effect when laser light reflected from a moving target re-enters the laser cavity and causes phase dependent changes of the lasing intensity. A piezo positioner was used to displace the interferometer with known frequency and amplitude as a basis for real-time calibration of the interferometer's sensitivity. The signal-processing algorithm is described that allows measurements in presence of high amplitude noise leading to variation of the interferometer's operating point. Measurements of sound-induced basilar membrane displacements were made in the intact cochleae of rodents by focusing the laser beam of the interferometer through the transparent round window membrane. The interferometer provides a viable means for making subnanometre mechanical measurements from structures in the inner ears of small mammals, where opening of the cochlea is not practicable.

Algorithms↗