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PubMed1997

Focal microcirculation disorder induced by photochemical reaction in the guinea pig cochlea.

A small region of microcirculation disorder in the cochlea of the guinea pig could be induced by a photochemical reaction. Photoillumination to the cochlea was done after systemic infusion of Rose Bengal (RB). The lateral wall of the second or third turn of the cochlea was illuminated for 10 min with a 1 mm diameter focused green light supplied by a xenon lamp. Degeneration of the stria vascularis (SV) was observed by a scanning electron microscope at 60-300 min after illumination. The range of length of degenerated area in the SV was from 111 to 1800 microns, with a mean of 760 microns. The organ of Corti along the illuminated lesion of the SV was well preserved in all animals at 60-300 min. In contrast, degeneration of sensory hair cells and scar formation in the SV were observed in the focal lesions of the three animals killed 1 week after illumination. The increase of diameter in the vessel of the SV from the radiating arteriole, the vessel of basilar membrane (VSBM) and limbus vessel (LVS) were observed in the illuminated area with diaminobenzidine (DAB) staining. These findings suggest that segmental microcirculation damage occurred in the SV and modiolus. In physiological studies, compound action potentials (CAP) were evaluated. Endocochlear potentials (EP) were also measured at the second turn under three different situations (groups A, B and C). A photochemically induced lesion was created at the site of EP measurement (group A), a site in the second turn 1 mm from the EP measurement site (group B) and a site in the third turn adjacent to the EP measurement site (group C). Threshold shift of CAP (up to 5.6 +/- 1.8 dB SPL) and reduction of EP (down to 11.4 +/- 10.7 mV) in the photochemically injured location were detected during about 15 min. EP did not recover to the predamaged level (79.9 +/- 3.7 mV) during 20 min. The morphological and physiological changes were not observed in the control group with illumination only. There were no significant decreases in EP values at the sites 1 mm from the lesion (group B) and at the inferior turn adjacent to the lesion (group C) compared to the marked decrease at the site of the photochemically induced lesion (group A). These findings suggest that CAP and EP are significantly affected by the interruption of segmental blood supply in the cochlea and remarkable decrease of EP occurs in the focal region of the guinea pig cochlea. We conclude that a localized blood circulation disorder induced by the photochemical reaction can make a focal lesion in guinea pig cochlea morphologically and physiologically.

Action Potentials↗

PubMed1989

Developmental alterations in the frequency map of the mammalian cochlea.

The position of an auditory hair cell along the length of the cochlea determines the sound frequency to which it is most sensitive. Receptors located near the proximal end (base) of the cochlea are maximally stimulated by high-frequency sounds; those occupying successively more distal (apical) positions respond best to progressively lower frequencies. At present, it is unclear how this frequency place map emerges with respect to the development of the cochlea. It has been suggested, on the basis of acoustic trauma experiments with developing chicks and cochlear potential recordings from developing gerbils, that this map may arise through systematic changes in the spatial encoding of frequency along the cochlea. Others have inferred from frequency tuning curves derived from auditory-nerve recordings in developing mammals and chicks, that the cochlear frequency-place map remains stable throughout development. We analysed frequency tuning curves obtained from gerbil spiral ganglion cells at a constant location within the basal cochlea, and report here that these cells undergo significant increases (up to 1.5 octaves) in their best-response frequencies between the second and third weeks of postnatal life. These recordings provide direct evidence for developmental changes in the tonotopic organization of the mammalian cochlea.

Acoustic Stimulation↗

PubMed2001

Localization of nitric oxide synthase isoforms in the human cochlea.

The location of nitric oxide (NO) in the structures of the cochlea is a topical issue. Nitric oxide synthase (NOS) has been detected previously in mammalian cochleae, but information on its presence in the human cochlea is still sparse. The location of NOS isoforms I, II and III in substructures of the human cochlea was studied by immunohistochemistry (fluorescein isothiocyanate technique) using monoclonal antibodies to NOS I, II and III. NOS I was the predominant isoform and staining could be observed in cells of the spiral ganglion (SG), in nerve fibres and in the outer hair cells (OHC). Furthermore, the supporting cells of the organ of Corti and the stria vascularis showed a fluorescent reaction to NOS I. Staining for NOS III was less intense and was located in the OHC, supporting cells and SG cells, while the stria vascularis remained unstained. By contrast, NOS II showed weak staining in a few neuron fibres only. The results imply that NO in the human cochlea could act as a neurotransmitter/neuromodulator at the level of neural cells and may be involved in the physiology of the supporting cells and stria vascularis. Moreover, because NO is both a mediator of excitotoxicity and a non-specifically toxic radical, it may also play a role in neurotoxicity of the human cochlea.

Adolescent↗

PubMed2003

Expression of mRNA encoding the H1, H2, and H3 histamine receptors in the rat cochlea.

Histamine may have physiological functions in the inner ear. Histamine receptors, however, have not yet been identified in the mammalian cochlea. We determined, using reverse transcription polymerase chain reaction (RT-PCR), that H1, H2, and H3 histamine receptor mRNA is expressed in the rat cochlea. To investigate the distribution of each receptor, the cochlea was divided into three parts: the lateral portion, the medial portion, and the modiolus. The mRNA for each receptor subtype was detected in the modiolus but not in the lateral and medial portions of the cochlea. This is the first evidence of H1, H2, and H3 histamine receptor mRNA in the rat cochlea. These findings support the suggestion that histamine may play a physiological role in the cochlea.

Animals↗

PubMed2006

Electrical resistivity measurements in the mammalian cochlea after neural degeneration.

OBJECTIVES/HYPOTHESIS: In the present series of experiments, the effect of neural degeneration on the cochlear structure electrical resistivities was evaluated to test if it alters the current flow in the cochlea and if increased current levels are needed to stimulate the impaired cochlea. In cochlear implants, frequency information is encoded in part by stimulating discrete populations of spiral ganglion cells along the cochlea. However, electrical properties of the cochlear structures result in shunting of the current away from the auditory neurons. This consumes energy, makes cochlear implants less efficient, and drastically reduces battery life. Models of the electrically stimulated cochlea serve to make predictions on current paths using modified and improved cochlear implant electrodes. However, one of the model's shortcomings is that most of the values for tissue impedances are not direct measurements. They are derived from bulk impedance measurements, which are fitted to lumped-element models. STUDY DESIGN: The four-electrode reflection-coefficient technique was used to measure resistivities in the gerbil cochlea. In vivo and in vitro (the hemicochlea) models were used. Measurements were made in normal and in deafened animals. Cochlear damage was induced by neomycin injection into the animals' middle ears. Neural degeneration was allowed to occur over 2 months before performing the measurements in the deafened animals. RESULTS: The resistivity values in deafened animals were smaller than in the normal-hearing animals, thus altering the current flow within the cochlea. CONCLUSIONS: Resistivity changes and subsequent changes in current path should be considered in future designs of cochlear implants.

Animals↗

PubMed2006

Tissue resistivities determine the current flow in the cochlea.

PURPOSE OF REVIEW: In individuals with severe to profound hearing loss, cochlear implants bypass normal inner ear function by applying electrical current directly into the cochlea, thereby stimulating cochlear nerve fibers. Stimulating discrete populations of spiral ganglion cells in cochlear implant users' ears is similar to the encoding of small acoustic frequency bands in a normal-hearing person's ear. Thus, spiral ganglion cells stimulated by an electrode convey the information contained by a small acoustic frequency band. Problems that refer to the current spread and subsequent nonselective stimulation of spiral ganglion cells in the cochlea are reviewed. RECENT FINDINGS: Cochlear anatomy and tissue properties determine the current path in the cochlea. Current spreads largely via scala tympani and across turns. While most of the current leaves the cochlea via the modiolus, the facial canal and the round window constitute additional natural escape paths for the current from the cochlea. Moreover, degenerative processes change tissue resistivities and thus may affect current spread in the cochlea. SUMMARY: Electrode design and coding strategies may result in more spatial stimulation of spiral ganglion cells, resulting in a better performance of the electrode-tissue interface.

Cochlea↗

PubMed2007

Ultrastructural changes of the cochlea after oral and maxillofacial firearm wounds.

BACKGROUND: There have been reports that maxillofacial firearm wounds could induce hearing loss. The effects on the ultrastructure of the cochlea and cochlear nerves after oral and maxillofacial firearm wounds are still unclear. This experiment investigates the ultrastructural changes of the cochlea and cochlear nerve after oral and maxillofacial firearm wounds. METHODS: Twenty dogs were wounded by steel spheres or detonators to establish animal models of oral and maxillofacial firearms wound. At different times after trauma, the wounds were examined and the specimens of the cochlea and cochlear nerve were taken to study the ultrastructural changes. RESULTS: The ultrastructural changes of the cochlea and cochlear nerve at 1 hour after trauma were cilia disorganization, edema of the nerve, and mitochondrial denaturalization. At 6 hours, there was extensive degeneration in the cochlea and cochlear nerve, cilia falling off of hair cells, and dissolution of the nerve sheath structure. CONCLUSIONS: The ultrastructure of the cochlea and cochlear nerve after injury is severe, but in the early period the injury is reversible.

Animals↗

PubMed2002

Possible roles of nitric oxide in the physiology and pathophysiology of the mammalian cochlea.

Nitric oxide (NO) has been implicated as a mediator of vasodilation and neurotransmission in the mammalian cochlea. This is demonstrated by the presence of nitric oxide synthase (NOS) and nitric oxide (NO) in the blood vessels and the organ of Corti in the cochlea. It is not certain if the neurons in the spiral ganglion produce NO since no fluorescent signal could be detected by 4,5-diaminofluorescein diacetate (DAF-2DA), a fluorescent indicator of NO. To determine if NO/peroxynitrite plays any role in neurodestruction observed in ischemic cochlea of the guinea pig, the effects of NO donors, such as S-nitrosocysteine (S-NC) and nitroglycerine (NTG); peroxynitrite generators, such as 3-morpholinosydnonimine (SIN-1); peroxynitrite inhibitors, such as superoxide dismutase plus catalase (SOD/Cat); and NOS inhibitors, such as N(G)-nitro-L-arginine methyl ether (L-NAME) were tested on normal and ischemic cochleae. The level of NO in the cochlea after 20 to 120 minutes of ischemia was indicated by measurement of nitrites/nitrates in the perilymph. The evidence gathered from these experiments indicates that NO or peroxynitrite is not necessarily destructive to auditory hair cells, and in fact, exogenous NO may protect neural structures in the cochlea from damage under ischemic conditions.

Animals↗

PubMed1997

Variation in expression of the outer hair cell P2X receptor conductance along the guinea-pig cochlea.

1. Whole-cell patch-clamp recordings were used to determine the variation in the P2X receptor conductance, activated by extracellular ATP, in outer hair cells (OHCs) isolated from each of the four turns of the guinea-pig cochlea. 2. In standard solution (containing 1.5 mM Ca2+) slope conductances were determined in OHCs of known origin from current-voltage relationships obtained from voltage ramps applied between -100 and +50 mV. Membrane conductance throughout this voltage range was greatest in OHCs originating from the basal (high frequency encoding) region of the cochlea. This gradient in OHC conductance from apex to base of the cochlea can be attributed to variation in expression of both a negatively activated K+ conductance and a TEA-sensitive outwardly rectifying K+ conductance. OHC slope conductance measured about a membrane potential of -75 mV increased from a mean of 33.5 nS in the apical region (turn 4) to 96.8 nS in the basal region (turn 1) of the cochlea. 3. Removal of external Ca2+ reduced OHC conductance by an average of 25%, reflecting a Ca2+ dependence of the background conductances in these cells. In zero external Ca2+ the mean slope conductance measured at -75 mV in the apical turn was 25.0 nS compared with 73.8 nS in the basal turn. 4. In Ca(2+)-free solution both 2 mM and 4 microM ATP produced inward currents that were progressively larger in OHCs originating from more basal regions of the cochlea. The steady-state inward current elicited by 2 mM extracellular ATP increased from -1.44 to -3.26 nA for turns 4 and 1, respectively. 5. The P2X receptor conductance was determined between -100 and +50 mV by comparing voltage ramps in the presence and absence of extracellular ATP in Ca(2+)-free solution. The conductance was inwardly rectifying with a reversal potential close to 0 mV. Measured close to the resting membrane potential of the cells (-75 mV), 2 mM ATP elicited an average 300% increase in conductance in parallel with the systematic increase in background conductance which occurs in OHCs originating from the more basal regions of the cochlea. The conductance at -75 mV activated by 2 mM ATP increased from a mean of 59.6 nS in turn 4 OHCs to a mean of 166.2 nS in turn 1 OHCs. The conductance activated by 4 microM ATP was also greater in the basal turn OHCs (45.3 nS) than in the apical region OHCs (5.9 nS). 6. The number of ATP-gated ion channels on individual OHCs, presumed to be localized to the stereocilia, increases from approximately 6000 in turn 4 cells to 16,500 in turn 1 cells, based on estimates of unitary conductance and average maximum ATP-activated OHC conductance (2 mM ATP).

Adenosine Triphosphate↗

PubMed2001

Mechanics of the mammalian cochlea.

In mammals, environmental sounds stimulate the auditory receptor, the cochlea, via vibrations of the stapes, the innermost of the middle ear ossicles. These vibrations produce displacement waves that travel on the elongated and spirally wound basilar membrane (BM). As they travel, waves grow in amplitude, reaching a maximum and then dying out. The location of maximum BM motion is a function of stimulus frequency, with high-frequency waves being localized to the "base" of the cochlea (near the stapes) and low-frequency waves approaching the "apex" of the cochlea. Thus each cochlear site has a characteristic frequency (CF), to which it responds maximally. BM vibrations produce motion of hair cell stereocilia, which gates stereociliar transduction channels leading to the generation of hair cell receptor potentials and the excitation of afferent auditory nerve fibers. At the base of the cochlea, BM motion exhibits a CF-specific and level-dependent compressive nonlinearity such that responses to low-level, near-CF stimuli are sensitive and sharply frequency-tuned and responses to intense stimuli are insensitive and poorly tuned. The high sensitivity and sharp-frequency tuning, as well as compression and other nonlinearities (two-tone suppression and intermodulation distortion), are highly labile, indicating the presence in normal cochleae of a positive feedback from the organ of Corti, the "cochlear amplifier." This mechanism involves forces generated by the outer hair cells and controlled, directly or indirectly, by their transduction currents. At the apex of the cochlea, nonlinearities appear to be less prominent than at the base, perhaps implying that the cochlear amplifier plays a lesser role in determining apical mechanical responses to sound. Whether at the base or the apex, the properties of BM vibration adequately account for most frequency-specific properties of the responses to sound of auditory nerve fibers.

Animals↗

PubMedDate not supplied

Time course of the endocochlear potential in the isolated cochlea of the guinea pig.

The temperature of Hanks' solution changed its potential (-0.48 mV/degrees C in Na(+)-Hanks' and -0.23 mV/degrees C in K(+)-Hanks' solution), but the pH had no clear effect on the potential. The time course of the endocochlear potential (EP) in the isolated cochlea of the guinea pig was measured under some different conditions. When the cochlea was moistened with Hanks' solution, negative EP increased gradually toward 0 mV at 124 min after death. When the cochlea was immersed in Hanks' solution, positive EP was obtained but it depended on the oxygen and the circulation of Hanks' solution. Moderate cooling (5 degrees C) of Hanks' solution had no significant effect on the EP of the isolated cochlea immersed in oxygen-saturated Hanks' solution circulated by oxygen bubbles. The space constant and the amplitude of the displacement responses were independent of the EP in the isolated cochlea. Thus, the positive EP might not show the physiological condition of the isolated cochlea.

Animals↗

PubMed2002

Expression of heat shock protein 70 in the cochlea in experimental autoimmune inner ear disease.

To explore whether the immune response of the inner ear could induce heat shock protein 70 (hsp70) in the guinea pig cochlea, we established a model of autoimmune inner ear disease (AIED) by systemically immunizing guinea pigs with homologous crude inner ear antigen (CIEAg). The immunized cochleas and normal control cochleas were examined for the expression of hsp70 by immunohistochemical analysis and in situ hybridization. It was found that 10 of 28 ears showed significant increases in hearing thresholds after the animals had been sensitized with CIEAg, and 67.9% of the ears from the immunized animals had modiolar vasculitis. The hsp70-like proteins were basically expressed in the normal cochleas, but dramatically increased expressions of hsp70 (perhaps also including hsp70-like molecules) and its messenger RNA were observed in the cochleas of the AIED models. The results suggest that the immune response of the inner ear induced the expression of hsp70 in the guinea pig cochleas.

Animals↗

PubMed1998

Thyroid hormone affects Schwann cell and oligodendrocyte gene expression at the glial transition zone of the VIIIth nerve prior to cochlea function.

All cranial nerves, as well as the VIIIth nerve which invades the cochlea, have a proximal end in which myelin is formed by Schwann cells and a distal end which is surrounded by oligodendrocytes. The question which arises in this context is whether peripheral and central parts of these nerves myelinate simultaneously or subsequently and whether the myelination of either of the parts occurs simultaneously at the onset of the cochlea function and under the control of neuronal activity. In the present paper, we examined the relative time course of the myelinogenesis of the distal part of the VIIIth nerve by analyzing the expression of peripheral protein P0, proteolipid protein and myelin basic protein. To our surprise, we observed that the expression of myelin markers in the peripheral and central part of the intradural part of the VIIIth nerve started simultaneously, from postnatal day 2 onwards, long before the onset of cochlea function. The expression rapidly achieved saturation levels on the approach to postnatal day 12, the day on which the cochlea function commenced. Because of its importance for the neuronal and morphological maturation of the cochlea during this time, an additional role of thyroid hormone in cochlear myelinogenesis was considered. Indeed, it transpires that this hormone ensures the rapid accomplishment of glial gene expression, not only in the central but also in the peripheral part of the cochlea. Furthermore, an analysis of the thyroid hormone receptors, TRaplha and TRbeta, indicates that TRbeta is necessary for myelinogenesis of the VIIIth nerve. Rapid thyroid hormone-dependent saturation of myelin marker gene expression in Schwann cells and oligodendrocytes of the VIIIth nerve may guarantee nerve conduction and synchronized impulse transmission at the onset of hearing. The thyroid hormone-dependent commencement of nerve conduction is discussed in connection with the patterning refinement of central auditory pathways and the acquisition of deafness.

Animals↗

PubMedDate not supplied

The vascular anatomy of the rat cochlea.

The vascular pattern of the rat cochlea was demonstrated by the aid of Berlin Blue (Prussian Blue) contrast. The vascular anatomy is similar to other mammals. The infrequent occurrence of the vessel of the basilar membrane under the organ of Corti is interesting in respect to its presumed importance for the oxygen supply to the hair cells. In the place where the vessel of the basilar membrane usually lies when present, a large uninjected channel was often seen throughout the cochlea. In the external wall, radiating arterioles supply and collecting venules drain all capillary areas. The vascular pattern of the external wall is well maintained at the basal end but is more sparse in apical parts of the cochlea as in other mammals. The rat cochlea is somewhat more difficult to manipulate than the cochlea in other mammals due to its small size, but the dissection of different parts of the cochlea was achieved without major problems.

Animals↗

PubMed1997

Effects of local anaesthetics on the gross receptor potentials in the guinea pig cochlea.

Local anaesthetics have been used intravenously and intratympanally to reduce tinnitus. In order to clarify its action in the periphery, we applied 0.5 mM tetracaine in the scala tympani in 18 cochleae and studied the effects on the receptor potentials. We used a temporal bone preparation of the guinea pig ear in vitro exposing the fourth cochlear turn where the cochlear microphonics (CM) and the summating potential (SP) were recorded. The perfusion was kept at a rate of 50 microliters/min. The frequency response of the cochlea was determined at the beginning of each experiment and the responses were recorded at the best frequency of the preparation. In another five cochleae an accumulated dose-response relationship was determined by increasing the tetracaine concentration in steps (50, 100, 300, 500, 1000 and 2000 microM), measuring the difference in amplitude of the receptor potentials. The CM decreased significantly (p < 0.001; mean 0.37 mV; SD 0.29). In 12 cochleae the SP was initially positive and did not increase significantly (p = 0.16; mean 0.07 mV; SD 0.16). In six cochleae the SP was initially negative and all changed polarity to positive and increased significantly (p < 0.05; mean 0.36 mV; SD 0.28). The effects on both the CM and the SP were reversible. Owing to the inter-individual variation between the cochleae the SP/CM ratio was determined and it increased significantly (p < 0.001; mean 0.18; SD 0.11). In the accumulated dose-response experiments the CM decreased significantly (p < 0.05) in a dose-dependent way, whereas the SP did not increase significantly. The SP/CM ratio increased significantly (p < 0.05) at 300 microM and 500 microM. We hypothesize that the peripheral tinnitus-reducing action of local anaesthetics is in part due to a reversal of the SP, but also to a reduction of the CM. The difference in effect of tetracaine on the receptor potentials, the CM and the SP, suggests that the SP is not dependent on the CM.

Anesthetics, Local↗

PubMed1998

[The technique of chronic infusion of drugs into the cochlea by an osmotic pump].

OBJECTIVE: To introduce a method of chronic infusion of drugs into the cochlea using a osmotic pump. METHODS: A stainless steel tube was surgically implanted into the basal turn of the chinchilla cochlea and connected to the pump. To assess the reliability of the procedure, and the pump, Hank's solution or L-buthionine-[S,R]-sulfoximine (BSO) was infused into the cochlea by this pump and inferior colliculus (IC) potential and hair cell morphology were examined. RESULTS: In three Hank's solution infused cochleas, the thresholds of IC potential were kept in the normal level and no hair cell loss was found 14 days after the beginning of the infusion, suggested that the pump implantation and Hank's solution infusion had no significant effects on the cochlear functions. In contrast, threshold shifts of IC potentials and hair cell loss were found in two BSO infused animals, suggested that the infused solution had distributed into the whole cochlea. CONCLUSION: This study indicates that the osmotic pump can be used in chronic delivery of experimental drugs into the cochlea.

Animals↗

PubMed2000

[Innervation of medial olivocochlear efferents in the cochlea of gerbils].

To explore the distributions of the medial olivocochlear (MOC) fibers and terminals in the cochlea of Mongolian gerbils and their physiological significance, a quantitative study on the distribution of MOC efferent fibers and terminals in whole cochlea of gerbils was performed using histochemical staining of acetylcholinesterase in the surface preparations. The relation between the density and size of MOC fibers and terminals in the cochlea and cochlear place-frequency map was analysed. The results were that the MOC fibers and terminals unevenly spreaded in the cochlea; the densest and the thickest MOC fibers and terminals were found in the distal part of the base turn and the second turn. These results demonstrate that the distribution of MOC fibers and terminals in the cochlea of gerbils is closely related to the function of frequency analysis of the cochlea.

Animals↗

PubMed1990

[An experimental study on the auditory brainstem response to electrical stimulation of the cochlea].

This animal research was undertaken to study some important issues for cochlear implantation. This included investigations of 1) the difference in the auditory brainstem responses (ABRs) to extra- and intracochlear electrical stimulations. 2) stimulus parameters and ABRs to a bipolar intracochlear stimulation, and 3) electrode placements and ABRs. There were no distinct differences in waveforms and input-output curves of ABRs between extracochlear electrical stimulation and intracochlear bipolar stimulation of the cochlea. Changes in amplitude and latency of ABRs were investigated at changes of the pulse amplitude or the pulse width of stimulating electric rectangular waves. Increase in the pulse amplitude or the pulse width resulted in increase of the amplitude of ABRs and no increase in the ABR latency. This results showed the amplitude of ABR was dependent on the amount of electricity; coulomb. Electrically evoked ABRs were studied for stimulations at different sites of the cochlea. The ABR elicited with a bipolar electrode placed at the third turn of the cochlea had a longer latency of each peak of ABR waves than the one at the basal turn. This indicates that electrical stimulation with a bipolar electrode can give rise to a localized excitation in the cochlea and a latency change along the longitudinal axis of the cochlea, so that it suggests a multichannel cochlea implant system can transmit more information as a spacious pattern than a single channel system.

Animals↗