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At least 235 records · Page 13Linked to original sources

PubMed1998

Effect of superior cervical ganglionectomy on catecholamine concentration in rat cochlea.

Both noradrenergic and dopaminergic nerve terminals have been described in the cochlea. The present report focused on the effect of superior cervical ganglionectomy (SCGx) on monoamine concentration in adult rat cochlea. In homogenates of whole cochleas, we measured the concentrations of norepinephrine (NE), dopamine (DA) and its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), by HPLC coupled to electrochemical detection. Measurements were carried out 4 h, 24 h or 6 days after unilateral SCGx. Most of the NE (approximately 82%) was lost after sympathectomy on the ipsilateral side, indicating that the principal localization of cochlear NE is in peripheral sympathetic fibers. Since about 18% of NE remained detectable 6 days after SCGx, a second origin of cochlear noradrenergic fibers may exist. Cochlear concentrations of DA or its metabolites did not change after SCGx. Therefore, DA and NE are located in two different populations of fibers within the cochlea, and are presumably related to distinct functional roles.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2002

Expression of members of Wnt and Frizzled gene families in the postnatal rat cochlea.

The functioning of the mammalian cochlea is entirely based on its mechanical properties, which are supported by a highly complex tissue architecture resulting from the precise arrangement of sensory hair cells and non-sensory supporting cells. Growing evidence indicates that evolutionary conserved signaling pathways are involved in inner ear development and in the differentiation of its diverse cell types. We investigated whether members of the Wnt and Frizzled gene families, which play key roles in a wide variety of cellular and developmental processes, are expressed in the postnatal rat cochlea. A PCR screening of a rat cochlea cDNA library performed with degenerate primers allowed us to isolate five members of the Wnt gene family (RWnt-2B, -4, -5A, -5B, and -7A) and six members of the Frizzled gene family (Rfz1, Rfz2, Rfz3, Rfz4, Rfz6, Rfz9). In situ hybridization and immunocytochemistry experiments demonstrated that RWnt-4, -5B, -7A have distinct, although partly overlapping, expression patterns in the juvenile rat cochlea. These results suggest that the Wnt-Frizzled signaling pathway could be involved in several aspects of late cochlear differentiation and/or auditory function.

Aging↗

PubMed1999

Selective expression of serotonin receptor transcripts in the mammalian cochlea and its subdivisions.

Expression of serotonin receptor (5-HTR) mRNA has been determined in the mammalian cochlea and its subdivisions by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Specific primers targeting individual 5-HTRs 1-7 directed amplification of 5-HTR subtypes 1A, 1B, 2B, 2C, 3, 5B, and 6 from mouse cochlea cDNA. No evidence of expression was obtained for 5-HTRs 1D, 2A, 4 (L and S), 5A, and 7. The distribution of receptor mRNA within the cochlea was determined with application of RT-PCR to morphologically defined microdissected subfractions of the rat cochlea. Messages for 5-HTR subtypes 1A, 1B, 2B, and 6 were present in the organ of Corti, lateral wall, and spiral ganglion subfractions. Messages for 5-HTR subtypes 2C, 3 and 5B were found in the spiral ganglion, but not in the organ of Corti or lateral wall fractions. The existence of transcripts for 5-HTRs 1A, 1B, 2B and 6 in the organ of Corti is consistent with a role for these receptors in serotonin-mediated modulation of the mechanosensory signal.

Animals↗

PubMed1996

Systematic approach to electrode insertion in the ossified cochlea.

Ossification of the fluid spaces of the cochlea occurs often in candidates for cochlear implantation, especially children. When noted before surgery on computerized tomography, ossification previously was thought to contraindicate cochlear implantation because of possible mechanical obstruction and uncertainty about the level of function that could be achieved by stimulating an ossified cochlea. However, during the preceding 6 years, techniques have been developed that permit implantation in ossified cochleas. We present a systematic approach that has been developed to treat the three clinically important categories of cochlear ossification: round window niche obliteration, inferior segment obstruction, and upper segment obstruction. Case reports are presented for each of these three drill-out procedures, demonstrating results often similar to those expected for implantation of the nonossified cochlea.

Adult↗

PubMed1997

Pattern of synaptophysin immunoreactivity in the efferent nerve terminals of the guinea pig cochlea.

The goal of the present study was to analyze the distribution of efferent 8th nerve synaptic endings in a surface preparation of the guinea pig cochlea using synaptophysin antibodies. Employing light and confocal microscopy synaptophysin immunoreactivity was found exclusively at the base of the outer hair cells (OHCs) and the inner hair cells (IHCs) axosomatic efferent synapses. Qualitative and quantitative differences were found between the OHCs and the IHCs immunoreactivity. Efferent nerve endings innervating IHCs were comparatively smaller, more numerous and densely packed. Efferent terminals demonstrated a longitudinal gradient for the IHCs and a longitudinal and radial gradient for the OHCs. Quantitative analysis of synaptophysin immunofluorescence demonstrated a higher percentage of efferent terminals innervating the IHCs and the OHCs in the mid and basal segments of the cochlea than in the apical regions. In addition, a radial gradient from the 1st to 3rd row of OHCs was evident. The results from the present study show that the analysis of synaptophysin immunoreactivity on cochlear surface preparations allows the efferent innervation to be determined throughout the entire cochlea. This technique allows for a rapid assessment of the normal cochlea as well as after cochlear insult.

Animals↗

PubMed1998

The use of 3D conformal radiotherapy (3D CRT) to spare the cochlea in patients with medulloblastoma.

PURPOSE: Radiation therapy in combination with cis-platinum chemotherapy is associated with ototoxicity due to destruction of cochlear hair cells. This is a significant problem, especially in pediatric patients, because it may lead to difficulties with communication, speech, language, and development of learning skills. The use of 3D conformal radiotherapy (3D CRT) may be useful in sparing auditory structures. This paper discusses a technique using 3D CRT to spare the cochlea in patients with medulloblastoma. METHODS AND MATERIALS: Five pediatric patients with medulloblastoma were planned using 3D CRT. All had MRI and CT obtained specifically for treatment planning. Multiple structures were contoured, including the cochlea and posterior fossa, and conformal beams designed in beam's eye view and dose distribution analysis were edited to provide 3D dose coverage to the target while sparing the inner ear. Patients received 36 Gy to the craniospinal axis followed by an 18-20 Gy boost to the posterior fossa. RESULTS: A 3D CRT cochlear sparing technique was designed, using an axial pair of posterior oblique fields to treat the posterior fossa while sparing the cochlea for all patients in this analysis. Dose-volume information, obtained from 3D calculations, demonstrates that the average dose received by the cochlea was 65% of the prescribed dose using the cochlear sparing plan, as compared to 101% using standard opposed-lateral beams. Both plans delivered > or = 100% of the prescribed dose to the posterior fossa. CONCLUSION: 3D CRT allows for cochlear sparing in the treatment of medulloblastoma. Further follow-up is necessary to determine the long-term benefit in these patients.

Cerebellar Neoplasms↗

PubMed2003

Structure and innervation of the cochlea.

The role of the cochlea is to transduce complex sound waves into electrical neural activity in the auditory nerve. Hair cells of the organ of Corti are the sensory cells of hearing. The inner hair cells perform the transduction and initiate the depolarization of the spiral ganglion neurons. The outer hair cells are accessory sensory cells that enhance the sensitivity and selectivity of the cochlea. Neural feedback loops that bring efferent signals to the outer hair cells assist in sharpening and amplifying the signals. The stria vascularis generates the endocochlear potential and maintains the ionic composition of the endolymph, the fluid in which the apical surface of the hair cells is bathed. The mechanical characteristics of the basilar membrane and its related structures further enhance the frequency selectivity of the auditory transduction mechanism. The tectorial membrane is an extracellular matrix, which provides mass loading on top of the organ of Corti, facilitating deflection of the stereocilia. This review deals with the structure of the normal mature mammalian cochlea and includes recent data on the molecular organization of the main cell types within the cochlea.

Animals↗

PubMed2000

Influence of pulsed laser irradiation on the morphology and function of the guinea pig cochlea.

Recent experimental and clinical studies have demonstrated that several pulsed laser systems are also suitable for stapedotomy. The aim of the study was to investigate morphological and functional inner ear changes after irradiating the basal turn of the guinea pig cochlea with two pulsed laser systems of different wavelengths. The Er:YSGG (lambda=2.78 mcm) and Ho:YAG (lambda=2.1 mcm) lasers were used applying the laser energies necessary for perforating a human stapes footplate. The cochleas were removed 90 min, 1 day, 2 weeks, or 4 weeks after laser application. Acoustic evoked potentials (compound action potentials) were measured before and after laser application and at the above times immediately before removal of the cochleas. The organ of Corti was examined by scanning electron microscopy. Application of Er:YSGG laser parameters effective for stapedotomy had no adverse effects on Corti's organ in the guinea pig cochlea. On the other hand, effective Ho:YAG laser parameters cause damage to the outer hair cells with fusion of stereocilia and formation of giant cilia leading to partial or total cell loss. The inner hair cells and supporting cells were usually normal. These morphological data show a good correlation with the electrophysiological measurements. Our results clearly demonstrate that, besides achieving efficient bone management, the Er:YSGG laser has high application safety. On the other hand, the Ho:YAG laser is not well tolerated in our animal study. Its use in stapedotomy would be unreliable and dangerous for the inner ear.

Action Potentials↗

PubMed2001

Carboplatin-induced oxidative stress in rat cochlea.

Carboplatin is currently being used in the clinic against a variety of human cancers. However, high dose carboplatin chemotherapy resulted in ototoxicity in cancer patients. This is the first study to show carboplatin-induced oxidative stress response in the cochlea of rat. Male Wistar rats were divided into two groups of six animals each and treated as follows: (1) control (normal saline, i.p.) and (2) carboplatin (256 mg/kg, i.p.). Animals in both groups were sedated with ketamine/xylazine and auditory brainstem-evoked responses were recorded before and 4 days after treatments. The animals were sacrificed on the fourth day and cochleae were harvested and analyzed. A significant elevation of the hearing threshold shifts was noted at clicks, 8, 16, and 32 kHz tone burst stimuli following carboplatin administration. Carboplatin significantly increased nitric oxide and malondialdehyde levels, xanthine oxidase and manganese-superoxide dismutase activities in the cochlea indicating enhanced flux of free radicals. Cochlear glutathione levels, antioxidant enzyme activities such as copper zinc-superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase and enzyme protein levels were significantly depleted 4 days after carboplatin treatment. The data suggest that carboplatin induced free radical generation and antioxidant depletion, and caused oxidative injury in the cochleae of rats.

Animals↗

PubMed2004

Induction of heat shock protein 32 (Hsp32) in the rat cochlea following hyperthermia.

The genes for heat shock proteins (Hsps) can be upregulated in response to cellular trauma, resulting in enhanced cell survival and protection. Hsp32, also known as heme oxygenase 1, catalyzes the degradation of heme to produce carbon monoxide and bilirubin, which play a variety of cytoprotective functions at physiological concentrations, and iron, which is rapidly sequestered by the iron-binding protein ferritin. In the present study we examined the expression and localization of Hsp32 in the rat cochlea after heat shock using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunocytochemistry. Low levels of constitutive Hsp32 expression were observed in the normal rat cochlea by RT-PCR and Western blot. Hsp32 mRNA (messenger RNA) was present at higher levels in a subfraction containing sensorineural epithelium and lateral wall than in a subfraction containing modiolus. Western blot revealed that Hsp32 protein levels increase in the rat cochlea following heat shock. Immunocytochemistry showed scattered staining of outer hair cells in the organ of Corti of normal untreated rats. Following heat shock Hsp32 is upregulated in outer hair cells and the cells of the stria vascularis. These results suggest a potential role for Hsp32 as a component of the oxidative stress response pathway in the rat cochlea.

Animals↗

PubMed1996

Identification and cloning of site C splice variants of plasma membrane Ca-ATPase in the gerbil cochlea.

Plasma membrane Ca-ATPase (PMCA) gene products were identified in the gerbil cochlea by reverse-transcription polymerase chain reaction (RT-PCR). Cochlear cDNA was amplified using PMCA isoform-specific primers from splice site C, the calmodulin binding domain. PCR products were cloned and sequenced. The putative housekeeping PMCA genes, 1b and 4b, as expected, were present in the gerbil cochlea and shared 98.6 and 100% amino acid homology with published rat sequences, at splice site C, respectively. PMCA2b, 3a and 3b splice variants also were detected in cochlear cDNAs and shared 95, 94.3 and 98% amino acid homology with their rat counterparts. PMCA isoforms 2 and 3 have been shown to occur in highly specialized tissues, such as muscle and brain, that require finely tuned regulation of intracellular free Ca2+ levels. The presence of several isoforms and splice variants of PMCA in the cochlea most probably reflects their differential expression among the several cell types that have been shown to contain immunoreactive PMCA. This suggests that the cochlea has developed complex mechanisms that finely tune intracellular Ca2+ levels in different highly specialized cell types.

Amino Acid Sequence↗

PubMed1997

Expression and function of adenosine receptors in the chinchilla cochlea.

Previous studies indicate the presence of adenosine receptors in the cochlear tissues obtained from different animals. This study was initiated to determine the subtypes of adenosine receptor (AR) present in the chinchilla cochlea and to assess their function. Radioligand binding studies demonstrate the presence of both the A1AR and A3AR in membranes prepared from the cochlea, using the radioligands [3H]DPCPX and [125I]APNEA. Estimates of the number (Bmax) of A1AR and A1AR plus A3AR by saturation curves were 118 +/- 13 and 417 +/- 120 fmol/mg, respectively, with the respective equilibrium dissociation constants (Kd) averaging 2.7 +/- 0.2 and 26.3 +/- 13.8 nM. No significant number of A2aAR were detected using [3H]CGS21680. The nonhydrolyzable adenosine analog R-phenylisopropyladenosine (R-PIA, 1 microM) elicited a small but significant degree of inhibition of forskolin-stimulated adenylyl cyclase activity (10.4 +/- 2.5%) in cochlear membrane preparations, which was insensitive to blockade by theophylline (100 microM). Furthermore, R-PIA elicited an increase in inositol 1,4,5-trisphosphate production in dissociated cell preparations obtained from the cochlea. No significant effect of R-PIA was observed on auditory measures such as auditory brainstem evoked response, cochlear action potential and endocochlear potential following round window application. However, round window application of R-PIA elicited significant increases in the activities of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase and significantly reduced the levels of malondialdehyde, a marker of lipid peroxidation. These results suggest a potential cytoprotective role of adenosine in the cochlea against oxidative damage.

Adenosine↗

PubMed1997

Longitudinal endolymph flow associated with acute volume increase in the guinea pig cochlea.

Endolymph volume disturbances were induced by microinjections of artificial endolymph into the second turn of the guinea pig cochlea at rates less than 60 nl/min. Induced longitudinal movements and area changes of endolymph were quantified in the basal turn using an ionic flow marker technique. Tetramethylammonium (TMA) was used as a flow marker by iontophoresing it into endolymph in micromolar amounts. TMA movements in the apical and basal directions were monitored by ion-selective electrodes. Changes in endolymph flow and cross-sectional area of scala media were derived using a mathematical model to interpret the recorded tracer time courses. The model was validated by performing comparable volume injections and flow measurements in fine-diameter plastic tubes. The rate of flow of endolymph measured prior to injection was close to zero, in agreement with prior studies. Based on the injection of different volumes into endolymph over a 15 min period, we found that injection of up to 80 nl of artificial endolymph into the second turn would not induce flow in the basal turn. However, above this amount, flow towards the base increased at a rate which correlated with the injected volume, with endolymph moving basally by a distance of 0.0067 mm/nl of artificial endolymph injected. Flow rates measured in the third turn, on the apical side of the injection were far lower and showed characteristics consistent with there being no outlet at the apex. These results suggest that small volume disturbances are corrected locally in the cochlea, but larger disturbances produce a longitudinal flow of endolymph out of the cochlea which represents a significant mechanism contributing to homeostasis. It can be concluded that structures outside the cochlea, such as the endolymphatic sac, do play a role in the correction of endolymph volume disturbances. Although the maintenance of endolymph composition is dominated by local ion transport mechanisms, the capacity of these local mechanisms to maintain normal endolymph volume appears to be limited.

Animals↗

PubMed1999

Sensorineural hearing loss during development: morphological and physiological response of the cochlea and auditory brainstem.

We have investigated the effects of sensorineural hearing loss on the cochlea and central auditory system of profoundly deafened cats. Seventeen adult cats were used: four had normal hearing; 12 were deafened neonatally for periods of < 2.5 years (five bilaterally, seven unilaterally); and one animal had a long-term (approximately 8 years) profound bilateral hearing loss. Bipolar scala tympani stimulating electrodes were bilaterally implanted in each animal, and electrically evoked auditory brainstem responses (EABRs) were recorded in an acute study to evaluate the basic physiologic response properties of the deafened auditory pathway. The cochleae and cochlear nuclei (CN) of each animal were examined with light microscopy. Spiral ganglion cell density in neonatally deafened cochleae was 17% of normal, and only 1.5% of normal in the long-term deaf animal. There was a 46% reduction in total CN volume in neonatally deafened animals compared to normal, and a 60% reduction in the long-term deaf animal. Neural density in the anteroventral CN of bilaterally deafened animals was 37% higher than normal; 44% higher in the long-term deaf animal. Significantly, however, we saw no evidence of a loss of neurones within the anteroventral CN in any deafened animal. There was a significant increase in EABR threshold and wave IV latency in the deafened animals, and a significant decrease in response amplitude and input/output function gradient. Again, these changes were more extensive in the long-term deaf animal. These data show that a sensorineural hearing loss can evoke significant morphological and physiological changes within the cochlea and auditory brainstem, and these changes become greater with duration of deafness. It remains to be seen whether these changes can be reversed following the introduction of afferent activity via chronic electrical stimulation of the auditory nerve.

Action Potentials↗

PubMed1999

Does electrical stimulation of deaf cochleae prevent spiral ganglion degeneration?

Thirty-six drug deafened guinea pigs were studied to determine how electrical stimulation of the cochlea affects spiral ganglion cell (SGC) survival. Animals were divided into two groups, extracochlear and intracochlear stimulation, and each group was further divided into four stimulus subgroups: no stimulation (implanted controls), the inferior colliculus electrically evoked potential (ICEEP) threshold-2 dB, ICEEP threshold+2 dB, and ICEEP threshold+6 dB. Stimuli consisted of 200 micros/phase charge balanced biphasic current pulses presented at 100 pulses per second using monopolar stimulation. Animals were stimulated 5 h/day, 5 days per week, for 8 weeks. The animals were then perfused and the cochleae serially sectioned at 4 microm saving every 8th section. We counted the number of intact SGCs, those containing a nucleus with chromatin, in each 20% segment of the cochlea and also measured SGC densities (number of neurons per mm2 of Rosenthal's canal). The number of surviving spiral ganglion neurons was not significantly different (P > 0.05) between the implanted and the unimplanted ears in any of the experimental groups. However, the spiral ganglion neuron densities were significantly elevated in the electrically stimulated ears (P < 0.001) but not in the implanted but not chronically stimulated ears (P > 0.05). We measured the volume of Rosenthal's canal in one subgroup (ICEEP threshold+2 dB) and found a decrease in this volume in the stimulated ear compared to the unstimulated ear (P < 0.01). These findings support the hypothesis that chronic monopolar electrical intracochlear or extracochlear stimulation is not a neurotrophic factor, increasing spiral ganglion neuron survival, but instead causes a narrowing of Rosenthal's canal that accounts for the increased spiral ganglion neuronal densities seen in the stimulated cochleae.

Animals↗

PubMed1999

Localization of the NO/cGMP-pathway in the cochlea of guinea pigs.

The presence of nitric oxide synthase (NOS) in substructures of the cochlea of guinea pigs is an issue of current focus. Moreover, information concerning the localization of cells effected by the NO/cGMP-pathway are rare. Paraffin sections of guinea pig cochlea were incubated with specific antibodies to the three known NOS isoforms, soluble guanylyl cyclase (sGC) and cyclic guanosine-monophosphate (cGMP), the second messenger system of NO. While detection of inducible iNOS failed in all cochlear structures, expression of endothelial eNOS was found in the spiral ligament, in the stria vascularis, in cells of the organ of Corti, in nerve fibers and in some perikaryia of the spiral ganglion. The cochlear nerve showed an accentuated affinity for immunostaining in distal, basal segments of the cochlea. Neuronal bNOS was found predominantly in the endosteum of the modiolus and cochlea and was less intensively present in all perikaryia of the spiral ganglion and in the spiral ligament. Supporting cells of the organ of Corti and cells in the limbus spiralis displayed only modest immunostaining, while bNOS was not found in outer and inner hair cells. NOS detection was accompanied by immunoreactivity to sGC and to cGMP. The presence of NOS and its second messenger system gives evidence for a possible involvement in neurotransmission, regulation of the cochlear amplifier and in homeostasis.

Animals↗

PubMed1999

Effects of a hair cell transcription factor, Brn-3.1, gene deletion on homozygous and heterozygous mouse cochleas in adulthood and aging.

The transcription factor Brn-3.1, is expressed in the inner ear hair cells throughout life and is necessary for the development of these cells. Mutant mice in which the Brn-3.1 encoding region has been deleted have no identifiable hair cells, greatly reduced numbers of spiral ganglion cells and are deaf. A mutation in the human homologue of this gene has been shown to be related to adult onset, sensorineural hearing loss (Vahava et al., 1998). The question whether haploinsufficiency in the mutant Brn-3.1 mouse with a mixed C57BL6/129Sv genetic background could affect the adult or aged cochlea was tested, therefore, by measuring the auditory brainstem responses and examining the cochlea's histologically at 2, 18 and 24 months of age. The heterozygotes had a comparable hearing to the wild-type animals and similar patterns of cochlear degeneration. Both groups showed an about 30 dB hearing loss beginning at 18 months of age, outer hair cell degeneration and loss of spiral ganglion neurons in the basal turn. There appeared to be no effect of Brn-3.1 haploinsufficiency on the mouse cochlea, implying that one intact copy of the gene is sufficient to maintain a normal cochlea.

Aging↗

PubMed1999

Survival-fixation of the cochlea: a technique for following time-dependent degeneration and repair in noise-exposed chinchillas.

To minimize problems with data interpretation due to interanimal variation in susceptibility to noise, we developed a survival-fixation paradigm which involves fixing one cochlea of an experimental chinchilla at one post-exposure time and fixing the second cochlea as much as 14-24 days later. This paradigm is analytically effective because there is a high correlation in the magnitude and pattern of damage in the left and right cochleas of binaurally exposed animals. Thus, each experimental animal provides two snapshots in the degeneration and repair continua in which it can be certain that both cochleas sustained equivalent amounts of damage during the exposure. Using this technique, the time course of degeneration of different structures and cells in the organ of Corti can be determined and primary damage can be distinguished from secondary effects. The present paper discusses the issues which had to be addressed to develop this technique and provides preliminary results from chinchillas exposed to a traumatic noise.

Animals↗