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Ornithine decarboxylase in the inner ear of the guinea pig.

L-Ornithine decarboxylase, the rate limiting enzyme of polyamine synthesis and a possible marker enzyme for tissue proliferation and maturation, has been found in the developing guinea pig cochlea using the unlabelled horseradish-peroxidase-antiperoxidase technique. Ornithine decarboxylase-like immunoreactive material was detected in the neurons of the Ganglion spirale and in their axonal and/or dendritic fibers. The location of the enzyme and the possible functional role of ornithine decarboxylase plays in the development and maturation of the auditory organ and of the hearing process are discussed.

Aging↗

Effects of loud tones on the inner ear: a combined electrophysiological and ultrastructural study.

Guinea pigs were exposed to a 10 kHz pure tone and damage to the cochlea was investigated immediately after exposure, or after a recovery period ranging from 18-25 days. Structural damage was assessed using scanning electron microscopy and functional damage estimated using the N1 threshold audiogram. Exposure at 106 dB for 1 h caused obvious abnormalities of outer hair cell stereocilia. The location and extent of this damage was related to the immediate or long term deficits in the N1 threshold audiogram.

Acoustic Stimulation↗

Specific pathology of the stria vascularis in postnatal progressive genetic inner ear disorder.

After reaching normal morphological maturation the stria vascularis of the Shaker-2 (Sh-2) mouse postnatally underwent a progressive degeneration, especially of the intermediate cell layer. Considerable changes were present on the 3rd week after birth. The marginal cells became atrophic and showed a reduction in the number and extent of the cellular extensions towards the intermediate cell layer. The intermediate cells disintegrated but were present 9 weeks after birth. The basal cells showed a normal morphology. Specific inclusion bodies were identified in the marginal cells from the 3rd week on. Occasionally such inclusions occurred in marginal cells. In the Shaker-1 (Sh-1) a flattening of intermediate cells occurred but otherwise no pathological changes were found 6--9 weeks after birth.

Age Factors↗

Structure of the barn owl's (Tyto alba) inner ear.

The basilar papilla of the Barn Owl's (Tyto alba) cochlea was found to be 9.5-11.5 mm long. Histological examination revealed that the sensory hair cells had a characteristic distribution: The proximal half contained mostly typical short cells; tall hair cells were present only on the distal half along with many short cells. Lenticular short cells occupied the proximal tip of the papilla. Another unusual feature of the proximal part was a dense fibrous mass in the basilar membrane. This was absent from the distal one-fourth.

Animals↗

Acetylcholinesterase activity in the embryonic chick's inner ear.

Putative cholinergic efferent endings, as demonstrated by the presence of a localized acetylcholinesterase reaction product and visualized by phase-contrast microscopy, appeared in the lagenar macula and cristae ampullares on the 11th embryonic day (ED) and in the basilar papilla by the 13th ED. During the course of development, the reaction product became denser and more sharply defined, reflecting the maturation of efferent endings.

Acetylcholinesterase↗

Cochlear preprocessing in analog models, in digital models and in human inner ear.

Data of spontaneous, delayed, and simultaneously evoked otoacoustic emissions produced in human subjects are compared with data produced in an analog and in a digital wave-parameter realization of our model. The high probability of the frequency distance of the emission's extreme values at 0.4 Bark, corresponding to a local distance of 0.5 mm along the basilar membrane is found also in the models. The influence of the lateral feedback coupling in the models on the frequency selectivity and on the appearance of emissions show the high quality of simulating human peripheral signal processing by the models.

Cochlea↗

The effects of DFMO on polyamine metabolism in the inner ear.

Difluoromethylornithine (DFMO) is a novel antineoplastic agent that was associated with an unexpected hearing loss in Phase II clinical trials. DFMO interferes with polyamine synthesis by inhibition of the enzyme ornithine decarboxylase (ODC). The objective of the current study was to establish a methodology to determine the effect of DFMO on polyamine levels and ODC activity in the cochlea. Guinea pigs received DFMO in their drinking water and were tested for auditory brainstem response threshold shifts. The organ of Corti, the lateral wall, and the acoustic nerve were assayed for both ODC activity and polyamine levels. In DFMO treated animals there was an inhibition of ODC activity in cochlear tissues as well as in intestinal mucosa. In addition, a significant depletion of cochlear polyamines was observed in the treatment animals. This study suggests that systemically administered DFMO inhibits ODC activity and interferes with polyamine synthesis in the cochlea.

Animals↗

Pilocarpine elicits the interdental cell secretory activity of the inner ear.

Subcutaneous injection of pilocarpine in guinea pigs resulted in the following ultrastructural changes: 1) the apical cavities of the interdental cells were filled with a substance indistinguishable from the overlying amorphous layer of the TM; 2) a great number of spherical structures appeared over the limbal portion of the tectorial membrane. In TEM photomicrographs these structures displayed the same appearance as the amorphous layer of the TM and were usually continuous to it; 3) the number of holes that decorate the upper surface of the limbal portion of the TM was dramatically increased and it was found that they connect the endolymphatic space to the apical cavities of the interdental cells; 4) there was an increase in the number of the small extracellular vesicles found in the clear spaces of the tectorial membrane. These facts suggest that pilocarpine stimulates the secretion of the interdental cells, confirming the existence of the secretory processes previously described (Prieto et al., 1990). These findings can be related to the turnover of the TM in the adult animal and, perhaps, to the secretion of some organic compound to the endolymph. We postulate that the actions of pilocarpine on the interdental cells are most probably mediated by the activation of muscarinic acetylcholine receptors in these cells.

Animals↗

The Na+/H+ exchanger in transitional cells of the inner ear.

The cytosolic pH (pHi) of transitional cells from the ampulla of the gerbil was measured micro-fluorometrically with the pH-sensitive dye 2',7'-bicarboxyethyl-5(6)-carboxyfluorescein (BCECF) to assess the possible contribution of a Na+/H+ exchanger to the regulation of pHi. All experiments were conducted in virtually HCO3(-)-free solutions. Under control conditions, pHi was 7.19 and addition of 10(-5) M ethylisopropylamiloride (EIPA), a blocker of Na+/H+ exchange, caused a small but significant acidification of pHi. A transient exposure to 21.4 mM NH4Cl caused a rapid cytosolic alkalinization followed by a brisk acidification and prompt recovery of pHi to its control value. The cytosolic buffer capacity (Bi) was determined in the absence of Na+ from changes in pHi which were elicited by [NH4+] steps. Bi was 4.7 mM/pH at pHi 7.19 and varied with pHi. The initial net proton flux JH, representative of Na+/H+ exchange activity, was calculated from the product of the initial rate of alkalinization after an NH4(+)-prepulse and Bi at the corresponding pHi. JH was dependent on the extracellular Na+ with an apparent Km of 64 mM, sensitive to the cytosolic [H+] with an apparent Km of 2.7 * 10(-7) M (i.e. pH 6.6), and inhibited by EIPA with an IC50 of 5 * 10(-7) M. These data suggest that transitional cells contain in the basolateral membrane a Na+/H+ exchanger of the amiloride-sensitive subtype.

Amiloride↗

High-resolution MR imaging of the inner ear: findings in Menière's disease.

Symptoms in Menière's disease are characterized by hydrops of the endolymphatic system with recurrent rupture of the membranous labyrinth. The primary cause of the increased endolymphatic volume appears to be an imbalance between secretion and resorption of the endolymph which may be due to an obstruction of the membranous endolymphatic duct and sac, located in the vestibular aqueduct. The membranous endolymphatic duct and sac are not expected to be visualized using conventional tomography and high-resolution computed tomography (HR-CT), whereas, these are identified with high resolution MRI (HR-MRI). By HR-MRI, we proposed to demonstrate morphological alternation in 12 patients with Menière's disease, this group was compared with a group of 20 healthy subjects. The degree of visualization on HR-MRI of the membranous endolymphatic duct and sac running through the vestibular aqueduct in the bony canal was assessed. There was a distinct decrease in visualization of the membranous endolymphatic duct and sac in the Menière's group. The results confirm the value of the HR-MRI technique to identify an anatomical abnormality, which is directly correlated with the lesion in cases of unilateral Menière's disease.

Adult↗

Anti-apoptotic role of retinoic acid in the inner ear of noise-exposed mice.

Exposure to loud noise can induce temporary or permanent hearing loss, and acoustic trauma is the major cause of hearing impairment in industrial nations. However, the mechanisms underlying the death of hair cells after acoustic trauma remain unclear. In addition to its involvement in cellular stress and apoptosis, the c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is involved in cell survival, transformation, embryonic morphogenesis, and differentiation. JNK is primarily activated by various environmental stresses including noise, and the phenotypic result appears be to cell death. All-trans retinoic acid (ATRA) is an active metabolite of vitamin A that regulates a wide range of biological processes, including cell proliferation, differentiation, and morphogenesis. We evaluated the role of ATRA in preserving hearing in mice exposed to noise that can induce permanent hearing loss. Mice fed with ATRA before and during 3 consecutive days of noise exposure had a more preserved hearing threshold than mice fed sesame oil or saline. Histological and TUNEL staining of the cochlea showed significantly enhanced preservation of the organ of Corti, including outer hair cells and relatively low apoptotic nuclei, in mice-fed ATRA than in mice-fed sesame oil or saline. Phospho-JNK immunohistochemistry showed that ATRA inhibited the activation of JNK. These results suggest that ATRA has an anti-apoptotic effect on cochleae exposed to noise.

Animals↗

The inner ear morphology and hearing abilities of the Paddlefish (Polyodon spathula) and the Lake Sturgeon (Acipenser fulvescens).

Concern regarding the spread of silver carp (Hypopthalmichthys molitrix) and bighead carp (Aristichthysc nobilis) through the Illinois River has prompted the development of an Acoustic Fish Deterrent (AFD) system. The application of this technology has resulted in a need to understand the auditory physiology of fish other than the target species, in order to minimise the effect of the AFD barrier on the ecology of indigenous fish populations. To this end, both the structures involved in sound reception and the hearing abilities of the paddlefish (Polyodon spathula) and the lake sturgeon (Acipenser fulvescens) are studied here using a combination of morphological and physiological approaches, revealing that both fish are responsive to sounds ranging in frequency from 100 to 500 Hz. The lowest hearing thresholds from both species were acquired from frequencies in a bandwidth of between 200 and 300 Hz, with higher thresholds at 100 and 500 Hz. The rationale for studying hearing in P. spathula and A. fulvescens in particular, is the value placed on them by both the commercial caviar producing industry and by the recreational fisheries sector. The hearing abilities of twelve P. spathula and twelve A. fulvescens were tested in sound fields dominated by either sound pressure or particle motion, with the results showing that acipenseriform fish are responsive to the motion of water particles in a sound field, rather than the sound pressure component. In this study, we measure the intensity of the sound field required to evoke threshold responses using a pressure sensitive hydrophone, as pressure dominated sound fields are the most audible acoustic condition for specialists like H. molitrix and A. nobilis (the target species). The results of the auditory examination clearly show that P. spathula and A. fulvescens are not sensitive to sound pressure, and will therefore have a significantly higher deterrent threshold than H. molitrix and A. nobilis in a pressure dominated sound field.

Acoustic Stimulation↗

Direct inner ear infusion of dexamethasone attenuates noise-induced trauma in guinea pig.

The protective effect of dexamethasone (DEX) against noise-induced trauma, as reflected in hair cell destruction and elevation in auditory brainstem response (ABR) sensitivity, was assessed in guinea pigs. The animals were administered DEX (1, 10, 100, and 1000 ng/ml) or artificial perilymph (AP) via a mini-osmotic pump directly into scala tympani and, on the fourth day after pump implantation, exposed to 120 dB SPL octave band noise, centered at 4 kHz, for 24 h. Animals receiving DEX demonstrated a dose-dependent reduction in noise-induced outer hair cell loss (significant at 1, 10 and 100 ng/ml DEX animals compared to AP control animals) and a similar attenuation of the noise-induced ABR threshold shifts, observed 7 days following exposure (significant at 100 ng/ml DEX animals compared to AP control animals). These physiological and morphological results indicate that direct infusion of DEX into the perilymphatic space has protective effects against noise-induced trauma in the guinea pig cochlea.

Animals↗

Effects of waveform shape on human sensitivity to electrical stimulation of the inner ear.

Psychophysical measures of the electrically stimulated human auditory system were obtained for different types of symmetric and asymmetric charge-balanced waveforms. Absolute detection thresholds of biphasic, pseudomonophasic, and 'alternating monophasic' current waveforms delivered by a bipolar intra-cochlear electrode pair were determined for four subjects implanted with the LAURA device. Thresholds for alternating monophasic stimuli, in which anodic and cathodic phases alternated every 5 ms, were 5-8 dB lower than for the biphasic waveforms for all four subjects. For two of the four subjects, thresholds for the pseudomonophasic waveforms were also significantly lower than for the biphasic waveforms. These pseudomonophasic thresholds were greatly affected neither by a 500-micros gap inserted between the two phases, nor by whether the shorter phase preceded or followed the longer one. Loudness balancing measures performed at the most comfortable levels also showed that, for equal loudness, alternating monophasic stimuli required a lower level than biphasic and pseudomonophasic waveforms. For three of the four subjects, the dynamic ranges of the pseudomonophasic (but not alternating monophasic) waveforms were greater than those of the biphasic waveforms. The results demonstrate that thresholds and dynamic ranges of human cochlear implant users can be controlled by manipulating the way in which the charge produced by the initial phase of an electrical pulse is recovered.

Adult↗