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Observations on the pattern of sensorineural degeneration in the human cochlea.

Cochlear sensory and neural degeneration was examined in nine pairs of human temporal bones fixed by perilymphatic perfusion, using phase-contrast and electron microscopy. Four pairs, three from females, had only slight sensorineural degeneration, limited to the very basal end of the cochlea. A predominantly neural degeneration was identified in a 54-year-old male. The process was bilateral, asymmetrical, uneven, and involved the entire length of the cochlea with several circumscribed areas of severe nerve degeneration. One case had mild, diffuse sensorineural degeneration in the lower half of the basal turn characteristic of presbyacusis. The other three pairs, all from males, revealed sensorineural degeneration patterns associated with noise injury and were remarkably similar to or almost identical with cochleas described previously. There was a good correlation between the presence of supporting cells and the survival of nerve fibres in the osseous spiral lamina in the corresponding area. In one cochlea, however, the degeneration of only inner hair cells in a small area was associated with complete nerve degeneration in the corresponding sector of the spiral lamina. Giant cilia were frequently seen in the apical turn.

Adult↗

Stimulation of residual hearing in the cat by pulsatile electrical stimulation of the cochlea.

Electrical stimulation of the cochlea may excite residual inner hair cells, either by direct electrical stimulation or through a mechanical event. Hair cell mediated responses of the auditory nerve to electrical stimulation were estimated from forward masking of the compound action potential evoked by an acoustic probe. Masking by a fixed electrical masker peaked for probes equal in frequency to the pulse repetition rate and its second harmonic, suggesting a spatially tuned profile of excitation within the cochlea. Furthermore, the tuning curves for masking of a fixed acoustic probe peaked for masker pulse rates close to the frequency of the probe. A secondary peak of masking was commonly seen for electrical stimulation at one half of the probe frequency, suggesting masking of the probe by the second harmonic of the electrical stimulus. These results suggest that pulsatile stimulation at the base of the cochlea generates a spectrally rich mechanical disturbance in which each component propagates to its place of resonance in the cochlea.

Acoustic Stimulation↗

Alpha 1-adrenergic receptors in the mammalian cochlea.

The presence of alpha 1-adrenergic receptors in the mammalian cochlea has previously been suggested by physiological experiments using antagonists specific to the receptor. However, the characteristics of adrenergic receptors in the cochlea have not been described. By employing [3H]-prazosin, high affinity, specific binding sites with characteristics of alpha 1-adrenergic receptors have now been identified and characterized in the chinchilla cochlea. Analysis of the specific [3H]-prazosin binding indicates that prazosin binds to a single class of high-affinity sites with a dissociation constant, kd, of 2.9 x 10(-9) M and a maximum number of binding sites, Bmax, of 30 fmol/mg dry tissue. Furthermore, the binding characteristics suggest that these receptors may be related to the microvasculature of the cochlea. These results provide a rational basis for the observed actions of alpha-adrenergic drugs on the auditory system.

Adrenergic alpha-Antagonists↗

Development of 11 beta-hydroxysteroid dehydrogenase expression in the rat cochlea.

11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyzes the transformation of active glucocorticoid (GC) steroids to inactive 11-oxosteroids, as well as the reverse reaction. 11 beta-HSD was previously demonstrated specifically in the spiral ligament of the lateral cochlear wall where it was co-localized with adrenal steroid receptors. These findings imply that 11 beta-HSD regulates binding of corticoids to their inner ear receptors. The GC receptor expression initially occurs around the critical maturation period of the cochlear duct. 11 beta-HSD, which is an integral part of the cochlear steroid receptor system, could indirectly affect glucocorticoid-mediated induction processes. In this study the expression of 11 beta-HSD was studied in the postnatal rat cochlea from the 3rd to 30th postnatal day. Bouin's fixed, paraffin-embedded cochlear sections were processed for immunocytochemical detection of 11 beta-HSD using polyclonal antibodies against 11 beta-HSD. 11 beta-HSD expression appeared at the 12th postnatal day at low levels in spiral ligament tissues. From the 15th postnatal day, 11 beta-HSD expression was stronger and similar to that of the adult cochlea. No additional inner ear tissue region expressed 11 beta-HSD enzyme during the observed period. 11 beta-HSD expression coincides with the onset of functional maturity of the rat cochlear duct. The expression of 11 beta-HSD is preceded by the expression of GC receptors which appeared at the 7th postnatal day in the rat cochlea. These results further suggest an integrative role of the cochlear steroid receptor system in the homeostasis and functional maturation of the cochlea.

11-beta-Hydroxysteroid Dehydrogenases↗

Microslicing of the resin-embedded cochlea in comparison with the surface preparation technique for analysis of hair cell number and morphology.

The surface preparation technique for hair cell counting is frequently used for the analysis of cochlear pathology in relation to hearing impairment. To overcome problems encountered with standard surface preparation methods, a new combination of resin embedding and microslicing has been applied to the mammalian cochlea, to permit hair cell counting to be followed by electron microscopic analysis. Partial removal of the cochlear shell is followed by resin infiltration under vacuum prior to polymerization. The cochlea is then subdivided into hemicoils using a mounted annular diamond blade. Embedding before microslicing ensures that both apical and basal regions of the cochlea are preserved equally well with an evenly distributed and therefore predictable 10% hair cell loss. By comparison, the standard surface preparation method often produces distortion of remaining organ of Corti and unpredictable losses of hair cells, for example, up to 17%. The damage tends to be greatest towards the base of the cochlea, an area which shows particular susceptibility to ototoxic agents such as the aminoglycoside antibiotics. Thus, for assessment of pathology caused by ototoxic agents, this method has considerable advantages over the surface preparation technique.

Animals↗

Fate of embryonic stem cells transplanted into the deafened mammalian cochlea.

Spiral ganglion neurons (SGNs), the primary afferent neurons of the cochlea, degenerate following a sensorineural hearing loss (SNHL) due to lack of trophic support normally received from hair cells. Cell transplantation is emerging as a potential strategy for inner ear rehabilitation, as injected cells may be able to replace damaged SGNs in the deafened cochlea. An increase in the number of surviving SGNs may result in improved efficacy of cochlear implants (CIs). We examined the survival of partially differentiated mouse embryonic stem cells (MESCs), following xenograft transplantation into the deafened guinea pig cochlea (n=15). Cells were delivered directly into the left scala tympani via microinjection through the round window. Small numbers of MESCs were detected in the scala tympani for up to 4 weeks following transplantation and a proportion of these cells retained expression of neurofilament protein 68 kDa in vivo. While this delivery method requires refinement for effective long-term replacement of damaged SGNs, small numbers of MESCs were capable of survival in the deafened mammalian cochlea for up to 4 weeks, without causing an inflammatory tissue response.

Animals↗

[Narrow-band action potentials of the guinea-pig cochlea as compared with the ordinary electrocochleograms under normal and pathological conditions].

The narrow-band action potentials (NAP) and the ordinary electrocochleograms were recorded from the guinea-pig cochlea under normal and pathological conditions in order to study whether the NAP could be a useful measure to detect cochlear dysfunctions. The cochlea damaged either by the administration of kanamycin or by a mechanical lesion of the round window served as pathological materials. Recordings showed that the threshold and amplitude measured for the N1 potential of NAPs ran in parallel with those of the cochlear microphonic potentials (CM), under both normal and pathological conditions of the cochlea. This implies that the CM could be replaced by the NAP when difficulties were present in recording CMs. It may be inferred that the NAP reflects responses of the inner hair-cells and cochlear nerves, while the CM would mainly be derived from responses of the outer hair-cells to the frequency-specific movements of the basilar membrane. If so, the NAP should offer a good means for the objective audiometry. Recording NAPs is also superior to the ordinary electrocochleography in that the method makes it possible to obtain responses generated near the apex of the cochlea, i.e., responses to low-pitch sound stimuli.

Action Potentials↗

[Distortion-product otoacoustic emissions in kanamycin-treated guinea pig cochlea].

Measurement of distortion-product otoacoustic emissions (DPOAE) is widely accepted as one of the most valuable tools for evaluating the frequency of specific cochlear pathology. Previous studies have revealed that distortion-product levels in the ear canal are definitely correlated with degree of damage in the cochlea. However, there seem to be no clear data of help in predicting the distribution and grade of damage in the cochlea quantitatively on the basis of the results of this non-invasive test. The present study is designed to assess correlations between degree of outer hair cell (OHC) damage by a potent ototoxic antibiotic, kanamycin, and DPOAE levels at the characteristic frequency at the site. Guinea pigs were used after daily intramuscular administration of kanamycin for 7 or 10 days. DPOAE levels were measured using a system (CUBDIS: Etymotic Research) with 78 frequency combinations of iso-intensity primaries from 0.5kHz to 16kHz of f2. The frequency ratio (f2/f1) was set at 1.2. Distortion-product level plots versus f2 (DP-grams) were constructed. The integrity of the OHC system was evaluated histologically by the succinic dehydrogenase (SDH) method under a light microscope. Cochleograms were constructed by calculating percentages of intact OHCs along the basilar membrane in 1-mm blocks. The DP-grams and the histopathological cochleograms showed essentially identical patterns in the kanamycin-damaged guinea pig cochlea. The results suggest that: 1) The generation of DPOAE requires functioning OHCs. 2) DPOAE measurement provides information allowing prediction of OHC damage distribution in the cochlea without histological investigations. 3) Careful setting of primary levels and other parameters is necessary to reliably predict the pathology. 4) Attempts to detect of minimal OHC damage could fail. 5) DPOAE seem very useful for monitoring cochlear function in clinically.

Animals↗

Centrifugal pathways protect hearing sensitivity at the cochlea in noisy environments that exacerbate the damage induced by loud sound.

Loud sounds damage the cochlea, the auditory receptor organ, reducing hearing sensitivity. Previous studies demonstrate that the centrifugal olivocochlear pathways can moderately reduce these temporary threshold shifts (TTSs), protecting the cochlea. This effect involves only the olivocochlear pathway component known as the crossed medial olivocochlear system pathway, originating from the contralateral brainstem and terminating on outer hair cells in the cochlea. Here I demonstrate that even moderate noise backgrounds can significantly exacerbate the cochlear TTSs induced by loud tones, but this is prevented because in such conditions there is additional activation of uncrossed olivocochlear pathways, enhancing protection of cochlear hearing sensitivity. Activation of the uncrossed pathways differs from that of the crossed pathway in that it is achieved only in noise backgrounds but can then be obtained under monaural conditions of loud tone and background noise. In contrast, activation of the crossed pathway is achieved only by binaural loud tones and is not further enhanced by background noise. Thus, conjoint activation of both crossed and uncrossed efferent pathways can occur in noise backgrounds to powerfully protect the cochlea under conditions similar to those encountered naturally by humans.

Acoustic Stimulation↗

Development of ganglion cell topography in the postnatal cochlea.

In mammals, the size and number of spiral ganglion cells can vary significantly along the length of the cochlea. At present, it is unclear how these topologic differences in spiral ganglion cell morphology and density emerge during development. We addressed this issue by quantifying developmental changes in the number, density, and size of auditory ganglion cells within the cochlea of Mongolian gerbils throughout the first 3 weeks of postnatal life. In each cochlea, cells were measured at five standardized locations along the length of the spiral ganglion, as determined from serial reconstruction of Rosenthal's canal. During the first postnatal week, the total number of gerbil spiral ganglion cells decreased significantly by 27%, without further change thereafter. This brief period of neuronal cell death coincides with a major remodeling in the afferent neural projections to gerbil auditory hair cells (Echteler [1992] Proc. Natl. Acad. Sci. USA 89:6324-6327). The resulting reduction in neuronal density varied with location, being most prominent within the upper basal and lower middle turns of the cochlea. These same regions contained the smallest auditory ganglion cells found within the gerbil ear and exhibited the least amount of developmental expansion in the circumference of Rosenthal's canal. These results suggest the possibility that regional differences in auditory neuron size and number might be influenced by local extrinsic factors, such as the availability of canal space.

Aging↗

[Protective effect of Radix Salvia Miltiorrhizae on radiation damage of the cochlea].

In order to evaluate the preventive and therapeutic effects of Radix Salvia Miltiorrhizae on radiation damage of the cochlea, guinea pigs were divided into 3 groups. Group 1 was treated by radiation added with Radix Salvia Miltiorrhizae. Group 2 was radiated alone, and Group 3 was control. Group 1 and Group 2 were radiated with a single dose of gamma radiation(60 Gy). Morphological and functional observation of the cochleae was performed in two weeks after radiation. The result showed that the changes of complex action potential(CAP) and the cochlear structure were slight in Group 1, but obvious changes were found in Group 2. There was a significant difference in CAP response threshold and incidence of the cochlear hair cell loss between Group 1 and Group 2 (P < 0.01). These results suggest that Radix Salvia Miltiorrhiza may prevent radiation-induced cochlea damage. Its protective mechanisms may be cleaning free radicals, blocking calcium channel and improving microcirculation of the cochlea.

Animals↗

[Safety of gene therapy within cochlea, experimental study with guinea pig].

OBJECTIVE: To observe the safety of inoculation of recombinant adenovirus with human neurotrophin-3 (Ad-NT3) into cochlea and its effect on hearing function. METHODS: Twenty healthy guinea pigs were randomly divided into two groups: ten animals were inoculated with Ad-NT3 into the perilymphatic space after a small hole was drilled in the bony wall near tympanic scala of the base turn, while the other ten were introduced with artificial perilymphatic fluid (APF) as controls. Auditory brainstem response (ABR) were recorded before, immediately after and seven days after the inoculation. Seven days after the surgery, the animals were killed. Frozen sections and colloidin sections of cochlea were made and observed under microscope. Immunohistochemistry was used to detect the expression of NT3 protein in cochlea. RESULTS: The mean ABR threshold values were (35 +/- 3.7) dB SPL and (35 +/- 3.2) dB SPL before the inoculation, (40 +/- 2.5) dB SPL and (40 +/- 3.0) dB SPL immediately after the inoculation, and (35 +/- 3.0) dB SPL and (35 +/- 3.0) dB SPL seven days after inoculation in the Ad-NT3 group and AFP group respectively (all P > 0.05). The ABR-III latency of 100dB SPL click was (2.812 +/- 0.087) ms and (2.824 +/- 0.121) ms before inoculation, (2.793 +/- 0.093) ms and (2.796 +/- 0.095) ms immediately after inoculation, and (2.822 +/- 0.102) ms and (2.834 +/- 0.135) ms seven days after inoculation in Ad-NT3 and AFP groups respectively (P > 0.05). No difference of ABR threshold and latency was observed at different time points in both groups. Ad-NT3 protein was expressed within each turn of the cochlea, including spiral limbus, spiral ligament and ganglion cells. The cochlear structure remained intact with no sign of infection or cell degeneration. CONCLUSION: Gene therapy by means of introduction of trace AdNT3 into the perilymphatic space through pore in tympanic scala is safe, causing no structure change or hearing loss.

Adenoviridae↗

[Local microcirculatory disorders in the cochlea basal turn near termination in guinea pigs].

OBJECTIVE: To study the characteristics of hearing loss caused by local microcirculatory disorders in the cochlea basal turn near termination of guinea pigs. METHOD: The local microcirculatory disorders in the cochlea basal turn near termination of guinea pigs were caused by photochemical reaction; morphological changes were observed by light microscope; the CAP N1 amplitude, CAP N1 latency and CAP N1 threshold shift which were evoked by short tone burst were recorded by Madsen 2250. RESULT: Morphological changes showed that histopathological changes were located in the basal turn near termination of cochlea. The CAP N1 amplitude, CAP N1 latency and CAP N1 threshold shift showed that the hearing loss was remarkable in the high-range frequencies. CONCLUSION: If the local microcirculatory disorders in the cochlea basal turn near termination take place, the hearing losses are more remarkable in the high-range frequencies.

Animals↗

[Isolation of outer hair cells from varying turns of the guinea-pig cochlea].

OBJECTIVE: To probe the method of isolating outer hair cells (OHC) from each of four turns of the guinea-pig cochlea. METHOD: From eight guinea pigs the organ of Corti from each of four turns of the cochlea were dissected, and then treated using enzyme. RESULT: A fair amount of living OHCs from each of four turns were obtained. The length of OHCs from each of four turns were 23.81, 34.50, 60.48 and 71.37 microns. CONCLUSION: The key to success in isolating OHCs from each of four turns of the cochlea is to know very well the anatomical characteristics of each of four turns of the cochlea and be operated in accordance with normal rules.

Animals↗

[The simultaneous isolation of outer hair cells and Deiters' cells from the cochlea of the guinea pig].

OBJECTIVE: To investigate the simultaneous method of isolating outer hair cells and Deiters' cells from the organ of Corti of the guinea-pig cochlea. METHOD: The organ of Corti was dissected from the pigmental guinea pig cochlea, and then treated with papain. RESULT: A large number of living outer hair cells and Deiters' cells were obtained synchronously from the guinea pig. CONCLUSION: The key to success in isolating outer hair cells and Deiters' cells from the cochlea is to know very well the anatomical characteristics of the cochlea and keep the contact the organ of Corti.

Animals↗

[Enzyme histochemistry study of non-focused ultrasound irradiating the cochlea in guinea pigs].

OBJECTIVE: To study the enzyme histochemistry changes of non-focused ultrasound (NFU) irradiating the cochlea in guinea pigs. METHODS: After 30 minutes or 8 hours of 2.5 MHz, 8 MHz NFU irradiating the cochlea in guinea pigs (70 ears) for 6 hours, the SDH activity of the hair cells of the cochlea was observed. RESULTS: The non-focused ultrasound (2.5 MHz or 8 MHz) irradiation for 6 hours has lad to enervation of the activity of SDH in hair cells, especially in outer hair cells, in the 0.87 +/- 0.20 mm areas of the second turn or in the 0.80 +/- 0.20 mm areas of the first turn, respectively. The activity of SDH can be part restorable in the 8 hours groups. CONCLUSION: NFU (2.5 MHz, 8 MHz) irradiating the cochlea for 6 hours can cause pathological changes in the hair cells of in different areas of cochlear. Moreover, the pathological changes could be restorable or part restorable in some amounts of NFU irradiation. The results suggest that the cochlear hair cell of the different area might be related to ultrasonic perception.

Animals↗

[Isolation of partial outer supporting cells from guinea pig cochlea].

OBJECTIVE: To investigate the method of isolating partial outer supporting cells (Deiters' cells, Hensen cells and Outer pillar cells) from guinea-pig cochlea and to try to establish the morphological criteria for these outer supporting cells viability. METHOD: The basal membrane was dissected from the pigmental guinea pig cochlea, and th incubated with enzyme (0.5 mg/ml), then mechanically trituated by micropipetee. RESULT: A large number of living Deiters' cells and Hensen cells could be obtained from the guinea pig cochlear which kept a good condition in the next eight hours. However, the isolated outer pillar cells, with a more vulnerable viability, had a low yield and degenerated in the followed five hours. CONCLUSION: The key to success in isolating outer supporting cells, mainly Deiters' cells and Hensen's cells, from the guinea pig cochlea is to familiarize with the anatomical characteristics of the cochlea and to get the intact organ of Corti, as well as to increase the concentration of enzyme. Moreever, the later four criteria for outer hair cells viability are also fit well for these isolated Deiters' cells, Hensen's cells and Outer pillar cells.

Animals↗

[The expression and significance of VIP and SP in the cochlea of rats].

OBJECTIVE: To investigate the expression of vasoactive intestinal peptide (VIP) and substance P (SP) in the cochlea of spontaneously hypertensive rat (SHR) and normal rat, and to evaluate the function of VIP and SP in the cochlea following the damage of hypertension. METHOD: The expression of VIP and SP in the cochlea of SHR was studied by immunohistochemical staining, and the mean optical density (OD) values of the positive fields were quantitatively examined by image analysis system. RESULT: The number of spiral ganglion cells at base turn in the hypertension group was significantly less than the normal (P < 0.01). VIP was expressed in the spiral ganglion cell plasm and stria vascularis of rats, so did SP. In spiral ganglion cell plasm the expression of VIP and SP had no significant difference between the two groups (P > 0.05); in stria vascularis the expression of VIP of the hypertension group was higher than the normal (P < 0.05). However, no significant difference in SP was found between the two groups. CONCLUSION: VIP not only contributes to regulate the cochlea microcirculation, but also acts as the neurotransmitter in the pathway of the auditory system. However, SP may be only a neurotransmitter in the pathway of the auditory system.

Animals↗