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PubMed2002

Complementary and layered expression of Ephs and ephrins in developing mouse inner ear.

The distributions of the Eph-class receptors EphA4 and EphB1, and their ligands ephrin-A2, ephrin-B1, and ephrin-B2, were analysed by immunostaining in the mouse inner ear. Complementary patterns of EphA4 and its potential ligand ephrin-A2 were found, with ephrin-A2 in many of the structures lining the cochlear duct and within the cochlear nerve cells, and EphA4 in the deeper structures underlying the cochlear duct and in the cells lining the nerve pathway. EphB1 and its potential ligands ephrin-B1 and ephrin-B2 showed a segregated layered expression in the lateral wall of the cochlear duct (the external sulcus), which together with EphA4 expressed in the area, form a four-layered structure with an alternating pattern of receptors and ligands in the different layers. This arrangement gives the potential for different bidirectional Eph-mediated interactions between each of the layers. The results suggest that the Eph system in the cochlea may have a role in maintaining cell segregation during phases of cochlear development.

Animals↗
PubMed1983

Anesthesia and surgical trauma: their influence on the guinea pig compound action potential.

A chronic implant consisting of a fine thermocouple placed on the round window permitted measurement of temperature and of the compound action potential (CAP) of the cochlear nerve in guinea pigs. Thresholds and latencies of the CAP, in response to tone bursts (2-40 kHz), were measured when the animal was awake and unrestrained, and again after several hours of anesthesia. The CAP remained unchanged with a variety of common anesthetics when precise control of round window temperature was maintained. However, when anesthesia was accompanied by several hours of slight cochlear cooling, thresholds were elevated for CAPs evoked by frequencies above 24 kHz and latencies were increased for CAPs evoked by all frequencies tested. The effects of surgery on CAP threshold and latency were also examined. Guinea pigs were tested while still anesthetized at the conclusion of the implantation procedure, and then again several days later while awake. Thresholds and latencies were unchanged. In two anesthetized guinea pigs already implanted with thermocouples, ventral and post-auricular surgery to expose the middle ear had no effect on the CAP, when low-speed drilling was used to open the auditory bulla. However, when small portions of the bulla were broken away with forceps, the CAP in response to high-frequency tone bursts immediately showed elevated thresholds. This alteration of the CAP was clearly different from that produced by lowered temperature, since the latencies at threshold were significantly decreased.

Action Potentials↗
PubMedDate not supplied

Electrophysiological studies of the auditory system.

Electrophysiological measures of cochlear function can be obtained using the techniques of transtympanic electrode and surface electrocochleography. These provide measures of the basic parameters of the cochlear microphonic, cochlear nerve and auditory brainstem nuclei action potentials, which enable the functional mechanisms of the cochlea and auditory pathway to be defined for normally hearing subjects and, by comparison, give diagnostic information about the pathologies involved in auditory disorders. Data are presented on the values and variability of the responses obtained from normally hearing subjects. The comparative values of each technique in estimating auditory threshold, cochlear function and in evaluating neurological conditions are discussed using data from clinical patients.

Acoustic Stimulation↗
PubMed2002

Vestibular schwannomas and auditory function: options in large T3 and T4 tumors?

OBJECTIVE: While hearing preservation has become an accepted treatment goal, there are still major doubts whether and to what extent this aim is feasible in large tumors that cover the auditory nerve and involve the brainstem. METHODS: One thousand eight hundred (1,800) vestibular schwannomas (VS) were operated on at Nordstadt Neurosurgical Department from 1978 to 1999 by the senior surgeon (MS). There were 1,800 tumors in 1,750 patients, 1,605 patients had unilateral tumors, 145 patients had neurofibromatosis type 2 with bilateral tumors, 195 of which were treated surgically in our unit. Preservation of the cochlear nerve was attempted when ever possible. The audiometric data are analyzed by Hannover Classification System graded in steps of 20 dB by audiometry and in steps of 10% to 30% by speech discrimination. Those data were set into relation with the Hannover tumor extension grading T1 to T4. RESULTS: Overall preservation rate was 40% with considerable differences, though, depending on the preoperative hearing quality and the tumor extension. Best results were obtained for intrameatal tumors (T1) with 56% and small intra-extrameatal tumors (T2) with 57% preservation rate. While preservation rate was at 44% in medium-sized tumors (T3), it was at 20% for T4 tumors with brainstem compression or even dislocation. However, satisfactory chances were encountered in cases with normal or good preoperative hearing, on average 54%, specifically 71% in T1, 69% in T2, 58% in T3 and 29% in T4. Regarding the quality of the preserved hearing, up to one third of cases in T1 and T2 may retain their preoperative hearing level, while this ranges around 20% for T3 and 10% to 14% in T4 tumors. DISCUSSION: For long, hearing preservation in medium sized or large tumors has not received any attention because of the presumed lack of realistic chances and the expected bad quality. Obviously, hearing preservation may be achieved in relevant numbers and at satisfactory quality levels. This aspects appears important to be addressed further in view of the fact that over 70% of tumors are presented for surgery at T3 or T4 extensions. CONCLUSION: The summit of hearing preservation has not been reached as improvements are still achieved even in most difficult conditions.

Cerebellopontine Angle↗
PubMed1982

[Tinnitus after microsurgical interventions at the internal auditory canal (author's transl)].

The preoperative and postoperative complaints of tinnitus of 126 patients were compared who had undergone microsurgery of the internal auditory canal. Evaluation of the questionnaires revealed that after section of the cochlear nerve in 11 cases of otherwise therapy-resistant tinnitus, total or partial relief was obtained in five of the patients. After surgery for cerebellopontine angle tumors (n = 46) or after neurectomy of the vestibular nerve of menière's disease (n = 34) tinnitus, in general, was neither initiated nor increased. Therefore, operations at the internal auditory meatus do not constitute a special risk with respect to iatrogenic generation of tinnitus.

Cochlear Nerve↗
PubMed1988

Modulation of cochlear tuning by low-frequency sound.

An intense, low-frequency tone (about 30 Hz) modulates the sensitivity of the inner ear to high-frequency stimulation. This modulation is correlated with the displacement of the basilar membrane. The findings suggest that the modulation may also affect cochlear tuning. We have investigated modulation of cochlear tuning by low-frequency sound in the guinea pig. Applying indirect methods of measurement (narrow-band analysis of compound action potentials and compound-action-potential tuning curves), the results suggest a shift of the excitation pattern along the basilar membrane towards higher-frequency areas. The shift occurred for both scala tympani and scala vestibuli displacement of the cochlear partition. Tuning curves, obtained from single units in the cochlear nerve, show sensitivity loss and a tip shift towards lower frequencies. This was also found for both scala tympani displacement and scala vestibuli displacement. The shift of the tip of the tuning curve towards lower frequencies corresponds to the inferred high-frequency shift of the excitation pattern. The relationship of these phenomena with the pathophysiology of Ménière's disease and with possible active mechanisms in cochlear transduction is discussed.

Animals↗
PubMed2002

Mechanisms of tinnitus.

The generation of tinnitus is a topic of much scientific enquiry. This chapter reviews possible mechanisms of tinnitus, whilst noting that the heterogeneity observed within the human population with distressing tinnitus means that there may be many different mechanisms by which tinnitus can occur. Indeed, multiple mechanisms may be at work within one individual. The role of the cochlea in tinnitus is considered, and in particular the concept of discordant damage between inner and outer hair cells is described. Biochemical models of tinnitus pertaining to the cochlea and the central auditory pathway are considered. Potential mechanisms for tinnitus within the auditory brain are reviewed, including important work on synchronised spontaneous activity in the cochlear nerve. Whilst the number of possible mechanisms of tinnitus within the auditory system is considerable, the identification of the physiological substrates underlying tinnitus is a crucial element in the design of novel and effective therapies.

Aminoglycosides↗
PubMed1996

Hearing results after posterior fossa vestibular neurectomy.

The effect of posterior fossa vestibular neurectomy on postoperative hearing levels of 172 patients was studied at 1 week, 1 month, 1 year, and 18 to 24 months. According to the 1985 American Academy of Otolaryngology-Head and Neck Surgery guidelines for reporting treatment outcome, 66% of patients had improved or unchanged hearing at 18 to 24 months. One-week postoperative hearing was poorer than at 1 month or later follow-up. Permanent profound hearing loss occurred in 4.7% of patients. In patients who had worse than 80 dB pure-tone average and 20% speech discrimination score hearing loss before surgery, 68% improved above this hearing level, and 16% improved to better than 50 dB pure-tone average and 50% speech discrimination after surgery. This suggests that it may be worthwhile to preserve the cochlear nerve in certain patients who may otherwise be candidates for labyrinthectomy. These hearing results are comparable with other treatment modalities including endolymphatic sac surgery.

Adolescent↗
PubMed1991

Distribution and targets of the cartwheel cell axon in the dorsal cochlear nucleus of the guinea pig.

This investigation attempted to determine the mode of distribution and synaptic targets of the cartwheel cell axon in the guinea pig dorsal cochlear nucleus (DCoN). Antiserum against PEP-19, a putative calcium-binding neuropeptide, was employed at the light and electron microscopic levels. We show that in the hind-brain of the guinea pig, cerebellar Purkinje cells and DCoN cartwheel cells are the most densely immunoreactive neurons. The PEP-19 immunoreaction product is localized to all neuronal compartments of these cells. Primary targets of cartwheel cell axons are the DCoN pyramidal cells, the large efferent neurons of layer 2. These neurons receive numerous immunoreactive synaptic boutons on their cell bodies and apical and basal dendritic arbors. A PEP-19-immunoreactive axonal plexus, largely formed by cartwheel cell axons, highlights layer 3, co-extensively with the basal arbors of pyramidal cells. This plexus is oriented predominantly in the transstrial plane of the DCoN, in parallel with the sheet-like basal dendritic arbor of pyramidal neurons and with the isofrequency bands of primary cochlear nerve fibers. PEP-19-positive boutons contain pleomorphic synaptic vesicles and form symmetric synaptic junctions, indicative of inhibitory innervation. In addition, immunoreactive boutons, similar to those synapsing on pyramidal neurons, were observed on the cell bodies and main dendritic trunks of cartwheel neurons, indicating a system of recurrent collaterals. Furthermore, a small number of PEP-19-positive axons of unknown origin reach the caudal rim of the posteroventral cochlear nucleus. Within the territory of distribution of the cartwheel cell axon are the dendrites of at least two other types of DCoN neuron, the vertical cells of Lorente de Nó and the giant cells. These neurons may represent additional targets of the cartwheel cell axon, but this remains to be ascertained with specific methods. Our data demonstrate that the cartwheel neurons modulate the activity of pyramidal neurons and, therefore, play a key role in shaping the output of the DCoN superficial layers.

Animals↗
PubMed1992

Topographic organization of the cochlear spiral ganglion demonstrated by restricted lesions of the anteroventral cochlear nucleus.

The morphological organization of the central projections of the cat cochlear spiral ganglion into the cochlear nucleus has been investigated by creating restricted lesions in the anteroventral cochlear nucleus (AVCN) in order to ablate selectively either the lateral or the medial aspect of isofrequency projection laminae. Such lesions induced highly selective retrograde degeneration of spiral ganglion cells. Ablation of the lateral part of the AVCN resulted in degeneration of cells within the scala tympani portion of the ganglion, whereas medial lesions within the AVCN induced degeneration of the scala vestibuli portion of the ganglion. Since most, if not all, of the primary afferent axons of the cochlear nerve bifurcate into ascending and descending branches as they enter the brainstem, it is noteworthy that selective damage to the ascending branch in the AVCN was sufficient to induce retrograde degeneration of the spiral ganglion cell somata. The peripheral and central axons also degenerated, and the losses of both the radial nerve fibers in the osseous spiral lamina and the central axons passing into the modiolus displayed selective topographies that paralleled the cell loss within the spiral ganglion. The results of this study support our previous hypothesis, based upon earlier horseradish peroxidase labeling experiments, that there is a topographic organization to the projection of the spiral ganglion within the isofrequency laminae that is orthogonal to the frequency representation within the ventral cochlear nuclei (VCN). That is, in addition to the spiral frequency organization of the ganglion, represented by the dorsal-to-ventral frequency map in the VCN, there is also an orderly and sequential distribution of inputs from the vertical (scala tympani-to-scala vestibuli) dimension of the spiral ganglion across the lateral-to-medial axis of the VCN. The interaction of these two topographic representations, distributed across the three dimensions of the VCN, must partly define the selective and/or integrative neuronal response properties at this first level of central nervous system processing of auditory signals within the cochlear nuclei.

Animals↗
PubMed1991

Morphometric analysis of developing neuronal geometry in the dorsal cochlear nucleus of the hamster.

Since the shape of a cell's dendritic field and the distribution of its input determine the information that a cell receives and transmits, it is important to ascertain how the spatial relations between axonal arbors and dendritic fields develop. This study investigates the development of the dendritic fields of fusiform cells in the dorsal cochlear nucleus. Golgi-impregnated cells from postnatal day 10, 15, 25, 45 and 60+ hamsters were reconstructed. The computerized morphometric system used analyzed cells in the plane of section and also allowed rotation to and analysis in other specified planes, such as that parallel to the terminal arbors of the cochlear nerve fibers. The results suggest that the apical dendritic fields are oriented parallel to the axis of cochleotopic organization and that this orientation develops gradually after birth. Dendritic growth is the result of addition of new dendritic branches. The angles between branches also change and were analyzed by viewing the dendritic fields in different planes. This revealed that some preferential expansion of the apical dendritic field in the plane parallel to the cochlear projection planes is the result of increased angles between branches in that plane. Thus, dendritic growth via the addition of branches and the 'fanning-out' of existing branches underlie the development of oriented dendritic fields.

Animals↗
PubMed2004

Effects of glucocorticoid receptor antagonist on CAPs threshold shift due to short-term sound exposure in guinea pigs.

OBJECTIVE: The steroid drugs are used for the standard treatment of sudden sensorineural hearing loss. However, clinical results on the effect of glucocorticoids in acoustic trauma have not yet been understood well. The effects of glucocorticoid receptor (GR) antagonist, mifepristone, on the cochlea sensitivity loss due to short-term sound exposure were studied in the guinea pig. METHODS: Mifepristone (20 mg/kg) was injected subcutaneously immediately after the noise exposure to 4 kHz pure tone of 100 or 120 dB SPL for 10 min and also at 1 day and 3 days later. Seven days after the sound exposure, the compound action potentials (CAPs) of the cochlear nerve and the 2f(1)-f(2) distortion product oto-acoustic emissions (DPOAEs) were recorded. RESULTS: No significant CAP threshold losses were observed in either mifepristone or saline administration after the exposure at 100 dB SPL. After the exposure at 120 dB SPL, administration of mifepristone elevated the CAP threshold at 5-8 kHz significantly as compared with the saline administration. The DPOAE output shifts of both saline and mifepristone groups were similar to each other. CONCLUSION: Mifepristone may influence inner hair cells (IHCs) and afferent nerve fibers beneath the IHC without having influence on outer hair cells (OHCs). It is suggested that glucocorticoid plays an important role in the improvement of hearing impairment after loud sound exposure.

Action Potentials↗
PubMed2000

Low-frequency acoustic modulations generated by the high-frequency portion of the cochlea, noninvasively recorded from the scalp of mice (Mus musculus).

Vocalizations often contain low-frequency modulations of the envelope of a high-frequency sound. The high-frequency portion of the cochlear nerve of mice (Mus musculus) generates a robust phase-locked response to these low-frequency modulations, and it can be easily recorded from the surface of the scalp. The cochlea is most sensitive to envelope modulation frequencies of approximately 500 to 2000 Hz. These responses have detection thresholds that are approximately 10 dB more sensitive than auditory brainstem responses, and they are very sharply tuned. These measurements may provide a nontraumatic means of repeatedly assessing cochlear functions involved in sound localization and perception of vocalizations.

Animals↗
PubMed1985

Hearing conservation surgery for acoustic tumors--a clinical-pathologic correlative study.

It has been estimated that hearing conservation is possible in 50% of patients with tumors extending medial to the porus acusticus 1.5 cm or less and who maintain speech discrimination scores of 80% or greater. Others have indicated that a hearing level of 30 dB or less and 80% discrimination are ideal candidates for hearing preservation surgery. Twenty-two cases of solitary schwannoma of the eighth nerve are reviewed in which adequate tissue was available for histologic fiber analysis, using the established preoperative predictive criteria for hearing preservation surgery. We describe the histology found in patients meeting these preoperative criteria. The tumors in ten cases measured less than 1.5 cm; five cases had a discrimination score of 80% or greater; and four cases had a pure-tone average of 30 dB or less. Only three cases satisfied any two criteria and only one case satisfied all three criteria. All cases had significant fiber destruction and tumor infiltration. The one case that met all three criteria demonstrated severe tumor infiltration within the cochlear nerve and the trunk of the eighth nerve; in two of five subserial en block tumor-nerve cross-sections no fibers could be identified crossing the tumor. Histologic data suggests that completely removing the tumor while attempting to preserve hearing may be beyond present surgical capabilities. They further suggest that the present preoperative criteria for selection of patients for hearing preservation are inadequate.

Cochlear Nerve↗
PubMed1991

Protein gene product 9.5 expression in the human fetal cochlea.

The distribution of protein gene product (PGP) 9.5 was analyzed in the human fetal cochlea using the indirect immunofluorescence method. In the 12- and 14-week-old human fetuses, the cells of the greater epithelial ridge and the lesser epithelial ridge were overall labelled with PGP 9.5, while the stria vascularis and the Reissner's membrane did not exhibit any staining. Spiral ganglion cells and cochlear nerve fibers were labelled with PGP 9.5 and PGP 9.5-positive nerve fibers made contact with the basement membrane of the Corti primordium in the 12-week-old human fetus. These results suggest that PGP 9.5 might be used as a histological marker of maturation and innervation in the human cochlea.

Biomarkers↗
PubMed2002

Tuning and timing in the gerbil ear: Wiener-kernel analysis.

Information about the tuning and timing of excitation in cochlear axons with low-characteristic frequency (CF) is embodied in the first-order Wiener kernel, or reverse correlation function. For high-CF axons, the highest-ranking eigenvector (or singular vector) of the second-order Wiener kernel often can serve as a surrogate for the first-order kernel, providing the same information. For mid-CF axons, the two functions are essentially identical. In this paper we apply these tools to gerbil cochlear-nerve axons with CFs ranging from 700 Hz to 14 kHz. Eigen or singular-value decomposition of the second-order Wiener kernel allows us to separate excitatory and suppressive effects, and to determine precisely the timing of the latter.

Acoustic Stimulation↗
PubMed2001

Elevation of internal auditory canal pressure by vestibular schwannomas.

OBJECTIVE: The exact mechanism of hearing loss, the most common presenting symptom in patients with vestibular schwannomas, remains unclear. To test whether increased pressure in the internal auditory canal from tumor growth is responsible for this clinical finding, the intracanalicular pressure in patients harboring these tumors was measured. STUDY DESIGN: Prospective study. SETTING: Tertiary referral hospital. PATIENTS: Fifteen consecutive patients undergoing a retrosigmoid approach for resection of vestibular schwannomas were included in the study. INTERVENTION: The intracanalicular pressure in every patient was measured by introducing a pressure microsensor into the internal auditory canal. The pressure readings, which were performed before tumor resection, were then correlated with tumor size and respective preoperative hearing status. RESULTS: Placement of the pressure monitor into the internal auditory canal revealed a biphasic waveform in every patient. Whereas the mean intracanalicular pressure was 20 mm Hg, there was significant variability among patients (range, 1-45 mm Hg). The intracanalicular pressure directly correlated with the amount of tumor in the internal auditory canal (r > 0.63, p < 0.012) but not with the total tumor size (r </= 0.40, p > 0.075). Furthermore, eight patients with class A preoperative hearing (American Academy of Otolaryngology-Head and Neck Surgery classification) had lower intracanalicular pressures than did five patients with class B hearing (16 +/- 5 vs. 28 +/- 4). Although this observation suggested an inverse correlation between the intracanalicular pressure and hearing function, the difference between the two groups was not statistically significant (p = 0.14). CONCLUSION: Pressure on the cochlear nerve as a result of tumor growth in the internal auditory canal may be responsible for hearing loss in patients with vestibular schwannomas. Modification of surgical techniques to address the elevated intracanalicular pressure may be beneficial in improving hearing preservation in these patients.

Cochlear Nerve↗