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PubMed1995

Potential distributions and neural excitation patterns in a rotationally symmetric model of the electrically stimulated cochlea.

In spite of many satisfactory results, the clinical outcome of cochlear implantation is poorly predictable and further insight into the fundamentals of electrical nerve stimulation in this complex geometry is necessary. For this purpose we developed a rotationally symmetric volume conductor model of the implanted cochlea, using the Boundary Element Method (BEM). This configuration mimics the cochlear anatomy more closely than previous, unrolled models. The calculated potential distribution in the cochlea due to stimulating electrodes is combined with a multiple non-linear node model of auditory nerve fibres, which we recently developed. The combined model is used to compute excitation profiles of the auditory nerve for a variety of stimulus levels and electrode positions. The model predicts that the excitation threshold, the spatial selectivity and the dynamic range depend on the exact position of the electrode in the scala tympani. These results are in good agreement with recently published electrical ABR data. It is shown that the use of actively modelled nerve fibres is essential to obtain correct predictions for the biphasic stimuli typically used in cochlear implants and that unrolling the cochlear duct as done in previous models leads to erroneous predictions regarding modiolar stimulation.

Animals↗
PubMedDate not supplied

Expression of the P2X7 receptor subunit of the adenosine 5'-triphosphate-gated ion channel in the developing and adult rat cochlea.

ATP-gated ion channels assembled from P2X(7) subunits have been implicated in ontogeny and cellular pathology. Here, the expression of the P2X(7) receptor subunit was studied in the embryonic (E14-E18 days) and postnatal (P0-adult) rat cochlea using immunohistochemistry. Strong P2X(7) immunolabelling was observed in the primary auditory neurons of the spiral ganglion from E18 to adult and in the fibres innervating the sensory inner and outer hair cells from birth to adult. Strong immunolabelling of P2X(7) receptor protein was also observed in the inner and outer hair cells over a limited developmental period, from birth to P6. Weak expression was observed in cochlear duct epithelium on E18 and in the supporting cells (footplates of pillar cells in adult and in Böttcher's cells after birth). The immunolocalisation of P2X(7) receptors further implicates extracellular ATP in signalling process in cochlear ontogeny and in establishment and function of auditory neurotransmission. The P2X(7) receptors may be involved in signal transduction and modulation as well as in regulating cell death during development and in pathological conditions.

Adenosine Triphosphate↗
PubMed1991

Pathogenesis and pathophysiology of Meniére's disease.

Meniére's disease, neither spontaneous nor inducible in animals, is studied only in patients. Natural history (epidemiology) shows a triad of major symptoms: vestibular, auditory, and aural pressure. One in 3 patients has bilateral Meniére's; over full lifespans, bilaterality approaches 50%. Aural pressure (74.1%) and positional vertigo during/between attacks (85.9%) are common. Clinical variants can persist for 25+ years. All forms have delayed onset and can occur years after incitement, after otosclerosis, infections like otitis media, syphilis, or trauma. Endolymphatic hydrops is found in all, most importantly in pars inferior (cochlear duct and saccule). Some (not most) cases show ruptures. The saccule can distend into the lateral semicircular canal. Symptomatic attacks are explained on physical/biochemical bases. Both longitudinal (slow) and radial (fast) flow seem operational, longitudinal in advanced Meniére's where membranous labyrinth replaces perilymph in scala vestibuli and vestibule. All forms result from endolymphatic absorptive dysfunction (in duct and sac), with mastoid and periaqueductal hypocellularity, hypodevelopment of Trautmann's triangle, and anterior displacement of lateral sinus. Secondary obstructions in ductus reuniens or utricolo-endolymphatic valve may explain atypical Meniére's (vestibular or cochlear alone).

Cochlear Diseases↗
PubMed1983

Response of cochlear potentials to presumed alterations of ionic conductance: endolymphatic perfusion of barium, valinomycin and nystatin.

Two models ('single-pump' and 'two-pump') of transepithelial potassium movement by the marginal cells of the stria vascularis have been proposed in the literature. Their validity was considered by exposing the endolymphatic (luminal) surface to agents (barium, valinomycin and nystatin) which are known to alter specific cellular membrane conductances in other tissues. This was accomplished by the use either of injections or of a relatively satisfactory technique for perfusion of scala media, which is described. Injection of barium caused the endocochlear potential (EP) to increase in normal animals and had no effect on the EP of deaf, Waltzing guinea pigs. Perfusion of the ionophores caused a decline in the EP in both normal and Waltzing guinea pigs. Only the 'two-pump' model (Na/K-ATPase-mediated cation pump on the basolateral membrane and rheogenic K transporter at the luminal membrane) is consistent with the results. The cellular heterogeneity of the cochlear duct, however, introduces a measure of uncertainty into this interpretation.

Animals↗
PubMed1991

Temporal pattern of nerve growth factor receptor expression in developing cochlear and vestibular ganglia in quail and mouse.

We have previously demonstrated the presence of specific receptors for nerve growth factor (NGF) in cochleovestibular ganglia of 72 h (stage 19-20) quail embryos, with a greater density of NGF receptors in the cochlear portion of the ganglion. The present study was conducted to determine the temporal pattern of NGF receptor expression in cochlear and vestibular ganglia throughout development, and was conducted in two species, quail and mouse. As in the quail, specific binding of 125I-NGF was detected in cochleovestibular ganglia of mouse embryos from an embryonic age equivalent to 72 h quail embryos (embryonic day 11, E11), with a similar concentration of 125I-NGF binding in the cochlear portion. Quantitative studies revealed that 125I-NGF binding continued to increase, in both cochlear and vestibular ganglia, for several days of development, and then began to decrease to minimal levels. Maximal levels were achieved at E7 in the quail, and E14 to E16 in the mouse, while minimal levels were reached by E13 in the quail, and E18 in the mouse. The level of 125I-NGF binding in cochlear ganglia was two to three times higher than in vestibular ganglia; a finding corroborated by radioautographic studies. In both quail and mouse, NGF receptors were more heavily concentrated in the ventromedial portion of the cochlear ganglion, adjacent to the cochlear duct; an area containing both support cells and peripheral neuronal processes. In the vestibular ganglion, 125I-NGF binding was more homogeneous, although small areas containing high densities of silver grains were observed. The presence of NGF receptors in cochlear and vestibular ganglia suggests that these ganglia may be responsive to and/or dependent upon NGF during their development.

Animals↗
PubMed1984

Support of cochlear metabolic and ion transport processes solely by perilymphatic perfusion.

Morphologic considerations would seem to suggest that the cochlear duct could not be maintained in a fully functional state in the absence of a blood supply. We found, however, that perilymphatic perfusion could be used as a substitute for the normal vascular circulation. The criteria used to determine cochlear function included (1) normal endocochlear potential, (2) normal net secretory flux of rubidium (as a tracer for K), and (3) normal levels of ATP in both the organ of Corti and the stria vascularis. All criteria were satisfied by our perfusion regimen.

Adenosine Triphosphate↗
PubMed1991

Expression of cytokeratin polypeptides during development of the rat inner ear.

The expression of cytokeratin polypeptides in the different epithelia of the developing inner ear of the rat from 12 days post conception to 20 days after birth was analysed immunohistochemically, using a panel of monoclonal antibodies. Throughout the development of the complex epithelial lining of the inner ear originating from the otocyst epithelium, only cytokeratins which are typical of simple epithelia were expressed. Cytokeratins 8, 18, and 19 were detectable shortly after the formation of the otocyst from the ectoderm (12 dpc), whereas cytokeratin 7 expression was delayed and first appeared in the vestibular portion and subsequently in the developing cochlear duct. During the development of the different types of specialized cells, differentiation-dependent modulation of the cytokeratin expression patterns was observed. In the mature inner ear, the specialized cell types displayed a function-related cytokeratin expression profile, both in the cochlear and vestibular portion. Cytokeratin expression in the flat epithelium of the vestibular portion suggests a more complex composition of this epithelium than has been established from routine morphology. Remarkably, the cochlear sensory cells were apparently devoid of cytokeratins, but no final conclusion could be drawn on the presence of cytokeratins in the sensory cells of the vestibular portion, because of the difficulty to delineate the cell borders between sensory cells and supporting cells.

Animals↗
PubMed1990

Anatomical model of the cochlea of the alligator lizard.

The three-dimensional structure of the cochlea of the alligator lizard was examined and an anatomical model was constructed. Separate pieces of the model represent the cochlear duct and posterior branch of the eighth cranial nerve. These pieces fit together inside a transparent plastic piece that represents the bony capsule. In this paper, the method used to construct the anatomical model is described, and three-dimensional features of cochlear anatomy are illustrated.

Animals↗
PubMedDate not supplied

Experiments on cochlear cryosurgery in the guinea pig. Light and surface microscopy.

The present investigation indicates that with cryosurgery it is possible to produce well defined cochlear lesions. The point of complete ablation can be chosen at will. A great advantage also is the fact that the bony capsule of the labyrinth is left intact. The remarkably slight scarring caused as well as the morphologically intact walls of the cochlear duct indicate an effective healing process, already completed after 6 days. These findings explain the unsuccessful clinical experiences when trying to ablate the labyrinth completely or to induce labyrinthine fistula with the help of cryosurgery (House, 1966). We suggest that for studies on cochlear function after exogenic trauma, cryosurgery gives easy reproductive morphological changes that may help the understanding and correlation of hair cell loss with cochlear physiology.

Animals↗
PubMed1996

Aetiology, prevalence and diagnosis of deafness in dogs and cats.

Peripheral deafness may be inherited or acquired, congenital or later-onset, and sensorineural or conductive. The most commonly observed forms are inherited congenital sensorineural, acquired later-onset sensorineural (ototoxicity, presbycusis) and acquired later-onset conductive (chronic otitis externa/media). In most dog and cat breeds inherited congenital sensorineural deafness results from perinatal degeneration of the stria vascularis, the vascular bed of the outer wall of the cochlear duct, which leads to hair cell degeneration. The strial degeneration appears to result from the absence of melanocytes, but their function in this structure is unknown. Ototoxicity may result from any of a large number of drugs and chemicals that directly or indirectly destroy cochlear hair cells. The effects are dose-dependent and in rare cases reversible. The most commonly recognized ototoxic drugs are the aminoglycoside antibiotics. Presbycusis, the ageing-related progressive hearing loss unattributable to other causes, is sensorineural but may also include mechanical changes in the tympanum and ossicles. Hearing aids may be accepted by some dogs as long as some residual function remains. Breeds reported to have been affected by congenital sensorineural deafness are listed and those with the highest prevalence are noted. Methods for diagnosis of deafness are described.

Animals↗
PubMed1998

Single unit recordings in the auditory nerve of congenitally deaf white cats: morphological correlates in the cochlea and cochlear nucleus.

It is well known that experimentally induced cochlear damage produces structural, physiological, and biochemical alterations in neurons of the cochlear nucleus. In contrast, much less is known with respect to the naturally occurring cochlear pathology presented by congenital deafness. The present study attempts to relate organ of Corti structure and auditory nerve activity to the morphology of primary synaptic endings in the cochlear nucleus of congenitally deaf white cats. Our observations reveal that the amount of sound-evoked spike activity in auditory nerve fibers influences terminal morphology and synaptic structure in the anteroventral cochlear nucleus. Some white cats had no hearing. They exhibited severely reduced spontaneous activity and no sound-evoked activity in auditory nerve fibers. They had no recognizable organ of Corti, presented >90% loss of spiral ganglion cells, and displayed marked structural abnormalities of endbulbs of Held and their synapses. Other white cats had partial hearing and possessed auditory nerve fibers with a wide range of spontaneous activity but elevated sound-evoked thresholds (60-70 dB SPL). They also exhibited obvious abnormalities in the tectorial membrane, supporting cells, and Reissner's membrane throughout the cochlear duct and had complete inner and outer hair cell loss in the base. The spatial distribution of spiral ganglion cell loss correlated with the pattern of hair cell loss. Primary neurons of hearing-impaired cats displayed structural abnormalities of their endbulbs and synapses in the cochlear nucleus which were intermediate in form compared to normal and totally deaf cats. Changes in endbulb structure appear to correspond to relative levels of deafness. These data suggest that endbulb structure is significantly influenced by sound-evoked auditory nerve activity.

Animals↗
PubMed1978

Two-tone suppression in auditory nerve of the cat: rate-intensity and temporal analyses.

Responses to two-tone stimuli were recorded from auditory-nerve fibers in anesthetized cats. One tone, the suppressor, was set at a frequency above characteristic frequency and was fixed in intensity. A second tone was set at an excitatory frequency and was varied in intensity. The suppressor tone, when set at a sufficient level, always reduced the response to the excitatory tone by an amount equivalent to a fixed number of decibels, regardless of the excitatory tone's intensity. Estimates of suppression magnitude were derived from shifts in rate-intensity function obtained when the suppressor tone was present relative to the functions obtained for the excitatory tone alone. When suppressor-tone intensity was increased, suppression magnitude likewise increased. When the two tones were increasingly separated in frequency, either by varying the excitor or by varying the suppressor, suppression magnitude decreased monotonically. Suppression behaved in the same manner regardless of whether suppresor tone was excitatory or nonexcitatory. When frequency separation was small enough and when both tones were above the neuron's characteristic frequency, responses synchronized to low-order combination tones could be elicited. These responses usually possessed different rate-intensity characteristics and resulted in estimates of suppression magnitude which were spuriously low. When frequency separation is normalized with regard to position of traveling wave maxima within the cochlear duct, the magnitude of two-tone suppression for a given suppressor-tone intensity is seen to be frequency independent.

Acoustic Stimulation↗
PubMed1978

The fate mapping of the eleventh and twelfth day mouse otocyst: an in vitro study of the sites of origin of the embryonic inner ear sensory structures.

An experiment was undertaken to determine which sensory structures of the mouse embryo inner ear developed from what portion of the mouse otocyst. Otocysts of gestation days 10, 11, 12, and 13 were divided by surgical dissection into six anatomical groups: dorsal, ventral, anterior, posterior, medial and lateral halves. They were organ cultured separately. After a period of ten days, the explanted tissues were harvested and processed histologically for microscopic analysis. The surgical control specimens fixed at the time of explantation were composed of undifferentiated ectodermal cells for tissues of gestation days 10, 11, and 12. Otocysts of gestation days 11, and 12 showed, during the course of their subsequent growth, that the three semicircular ducts and their associated cristae developed from the dorsal and lateral halves. Only the anterior and posterior canals and cristae originated from the medial portion. The posterior half gave rise to the posterior crista and the anterior half provided for the development of the anterior and lateral cristae. The cochlear duct and its sensory epithelium developed in all the anatomical groups except the dorsal half. The utricle developed in the dorsal section of the middle third of the otocyst, while the utricular macula developed in the anterior half of the same section of the otocyst. The saccule and its macula differentiated from the ventral section of the middle third of the anterior half.

Animals↗
PubMed2002

Biophysics of the cochlea - biomechanics and ion channelopathies.

Understanding how the cochlea works as a system has become increasingly important. We need to know this before integrating new information from genetic, physiological and clinical sources. This chapter will show how the cochlea should be seen as a device for carrying out a frequency analysis built from cells that have been adapted for specialist purposes. Sensory hair cells convert mechanical displacements into the neural code. The transducer channel remains to be identified. The biomechanics of the cochlear duct depends on an energy-dependent feedback from the sensory outer hair cells. The molecular basis for outer hair cell feedback depends on a protein that has recently been identified. The auditory signal encoded by the cochlea is further modified by membrane properties of the hair cells and cochlear supporting cells. The interplay between techniques of genetics, molecular biology and cell physiology has started to reveal which ion channels and transporters in the cochlea are mutated in certain forms of deafness. The interpretation of these mutations requires the cell physiology of the cochlear partition to be better characterised in the future.

Animals↗
PubMedDate not supplied

Acoustic and vestibular efferent neurons in the chicken (Gallus domesticus). A horseradish peroxidase study.

The origin of labyrinthine efferent fibres was investigated in the chicken. After injection of horseradish peroxidase (HRP) into the cochlear duct or into the ampulla of the horizontal semicircular canal, efferent neurons in the medulla oblongata were labelled by the granular reaction product of retrogradely transported HRP. Efferent vestibular neurons were found in the nucleus reticularis pontis caudalis bilaterally with more cells ipsilateral to the injection side, while efferent cochlear neurons could be demonstrated medial to the ventral division of the facial nucleus bilaterally with more neurons contralateral to the injection.

Animals↗
PubMed1999

Direct measurement of cerebrospinal fluid pressure through the cochlea in a congenitally deaf child with Mondini dysplasia undergoing cochlear implantation.

OBJECTIVE: Perilymph/cerebrospinal fluid (CSF) "gushers" may occur at cochleostomy during cochlear implant surgery, particularly in patients with congenital cochlear duct malformation in which CSF in the internal auditory meatus is in direct communication with the perilymphatic space in the cochlea. The object of the study was to measure the pressure and flow of a CSF gusher at cochleostomy. STUDY DESIGN: The design was a preoperative pressure measurement. SETTING: The setting was a multidisciplinary cochlear implant program. PATIENT: A 4-year-old girl with bilateral Mondini deformity undergoing cochlear implantation was studied. INTERVENTION: A size 23 FG intravenous cannula was inserted into the cochlea and connected to a pediatric drip set to form an improvised manometer. MAIN OUTCOME MEASURE: Intracochlear fluid pressure was measured at 14 cm H2O, equivalent to the normal CSF pressure that would be recorded in a child of this age at lumbar puncture. An indirect measurement of the likely size of the CSF/perilymph defect was made. RESULTS: This technique may allow better assessment of the risk of postoperative CSF leakage and meningitis. CONCLUSION: This simple technique of measuring the pressure in a perilymph gusher can be used to assess the need for careful sealing of the cochleostomy, to measure the reduction in pressure produced by head elevation or a spinal drain, and to assess the probable size of a defect in the lamina cribrosa.

Cerebrospinal Fluid Pressure↗
PubMed1976

[Computer technology in otospongiosis. 2. Statistics on 15 years of stapedectomy].

To complete their two previous data processing studies on systematization of parameters for otospongiosis and on statistics concerning the otospongiotic disease itself, the authors now develop the study of postoperative functional results obtained over 15 years stapectomies performed according to various techniques. The characteristic of this study is that the functional results are not considered only from the operative technique point of view, but that they also take into account all the factors having an influence upon the functional results, i.e. mechanical operative factors, otospongiotic cochlear factors and, finally the patient's general factor. This work is divided in three parts. The first part considers statistical data drawn from investigating elements taken over a period ranging from 1960 to 1975 from operative findings, surgical techniques and operative complications, particularly during reoperations, i.e., the mechanical part of hearing improvement in otospongiosis surgery. The second part deals with the problem of the medical postoperative care in stapedial surgery and with that of postoperative complications and the therapy used to combat them. It is the study of the cochlear support problem considering both the cochlear fragility facing the operative trauma, and the cochlear deterioration due to the enzymatic action of the otospongiotic microfoci of the lateral wall of the cochlear duct and of the vestibular side of the footplate. The third part is the statistical study made both by means of data processing and of manual investigation, on the long term functional results obtained, on one hand by the surgical solution of the stapedial fixation's mechanical problem, and on the other, by the medical solution of the cochlear problem considered both from the enzymatic and vascular point of view. This study of stapedectomies' long term functional results allows the authors to draw the conclusions which seem to result logically from this very elaborated statistical study concerning near 17000 stapedectomies performed from 1960 through 1975.

Audiometry↗
PubMed2000

Apoptosis in the developing rat cochlea and its related structures.

Mammalian development involves proliferation and programmed cell death (apoptosis). This study was undertaken to analyse the spatial and temporal organisation of apoptosis in developing rat cochlear and associated tissues using in situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling of DNA fragments (TUNEL), and light and electron microscopy. Embryonic (E12-E19 days) and postnatal rats (P0-P21 days) were studied. Fixed tissues were stained for apoptosis using TUNEL technique and the cytomorphology of apoptosis was confirmed by light and electron microscopy. Apoptotic cells were detected predominantly during the embryonic and early postnatal development of the cochlea. Apoptosis occurred in embryonic precursors of the cochlear duct epithelium, mainly in the region of its outgrowth between E12 and E16. In the periotic mesenchyme, apoptosis occurred in areas committed to develop into the middle ear cavity (peaking at E16) and perilymphatic compartments (peaking around E18-E19). Apoptosis in the VIIIth nerve (statoacoustic) ganglion was detected throughout the embryonic and early postnatal periods, peaking at E18-E19, around the time when the cochlear neural connections are being established. At later postnatal days, apoptosis was seen only occasionally in cochlear tissues, predominantly in tissues lining the middle ear cavity and sporadically in cells of the otic capsule. Therefore, apoptosis appears to occur in areas of remodeling, in areas of cavitation and in areas of differentiation. These findings provide a template for studying the molecular mechanisms involved in the development of the rat inner ear.

Animals↗