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At least 253 records · Page 14Linked to original sources

PubMed2000

Spatial expression patterns of epidermal growth factor receptor gene transcripts in the postnatal mammalian cochlea.

Recent in vitro studies demonstrated that members of the epidermal growth factor (EGF) family are involved in hair cell replacement in the postnatal mammalian organ of Corti (OC) after ototoxic damage. This suggests a role for the EGF receptor (EGFR) in this process. We examined the expression of EGFR mRNA within the normal postnatal day 3 (P3) and adult rat cochlear epithelium by RT-PCR and examined its cellular localization with non-radioactive in situ hybridization in P3 and adult cochleae. RT-PCR demonstrated that EGFR mRNA is expressed in P3 and adult cochlear epithelium. In situ hybridization localized high levels of EGFR transcripts in the OC, spiral ganglion, Kölliker's organ and detectable levels in the supporting cells and the stria vascularis of P3 cochlea. In the adult cochlea, EGFR transcripts were detected only in the spiral ganglion. Our results support that the EGFR is implicated in the differentiation of several cochlear cell types and in the response of OC to ototoxic damage of the P3 rat. In the adult, it may participate in the maintenance of the mature neurons and its absence in the OC may contribute to the lack of regenerative responses in the adult cochlea.

Animals↗

PubMed1999

A three-array cochlear implant: a new approach for the ossified cochlea.

The ossified cochlea, although rare, represents a challenge for cochlear implantation. While it is no longer considered an absolute contra-indication to implantation, insertion may be technically difficult and the results may be suboptimal. Techniques which have been employed are reviewed. The new Digisonic multi-array implant, which was designed specifically for use in the ossified cochlea is described, along with the technique used for its insertion. In the first patient to be implanted with this new implant, all electrodes lie within the cochlea and are functional. The new Digisonic multi-array implant may have advantages over other solutions for the ossified cochlea.

Adult↗

PubMed2003

Expression of G protein alpha subunits in the lateral wall of the rat cochlea.

Expression of five G protein alpha subunits was investigated in the rat cochlea by reverse transcription-polymerase chain reaction (RT-PCR) in order to understand their role in the cochlear signal transduction mechanisms. Immunohistochemical techniques were employed to study their distribution in the lateral wall of the cochlea. Total RNA was extracted with guanidine thiocyanate from cochleas and brains of 14-21-day-old rats. The extract was treated with DNase to degrade genomic DNA. After RT, the resulting cDNA was amplified by PCR using primers specific for the nucleotide sequences representing alpha subunits of heterotrimeric G proteins. The results indicated that mRNA for all five alpha subunits was expressed in the brain and cochlear samples. For immunohistochemical localization, temporal bones of 6-week-old rats were fixed in 4% paraformaldehyde and 0.1% glutaraldehyde and processed for embedding in paraffin wax. The dewaxed, midmodiolar sections of the cochlea were incubated with subunit-specific polyclonal antibodies. The pattern of immunoreactivity varied for the five G protein alpha subunits studied in the stria vascularis and spiral ligament. The significance of these findings and the role of G protein alpha subunits in cochlear fluid homeostasis are discussed.

Animals↗

PubMed2001

Immunohistochemical and morphological studies on the human fetal cochlea: a comparative view on methods.

The preservation of morphology and antigenicity can vary uncontrollably with human fetuses since these rely heavily on immediate fixation of the temporal bone following spontaneous abortion. Once good fixation is established, there is the question of the approach taken for morphologic and immunohistochemical studies. To achieve maximal preservation for the purpose of studying normal and pathologic fetal cochleae, commonly used preparation methods for analyzing the cochlea were reviewed and compared for both immunohistochemical and morphologic studies. Cochleae obtained after spontaneous abortion ranged from the 9th gestational week to birth. Four different methods were compared for morphologic study: the block surface method; a microslicing technique; paraffin; and celloidin sectioning. For immunohistochemical study, three methods were compared: pre-embedding; paraffin; and frozen sectioning. For morphologic preservation, the block surface method gave best overall results, showing good representation of the fetal cochlea for surface preparation, light, and electron microscopy. Celloidin sectioning was also found to show good light microscopic results for both the middle and inner ear. To achieve optimal results, preservation quality, fixation procedures, and antibody all contribute to the efficacy of a methods choice.

Antibodies↗

PubMed1994

[Experimental laser surgery of the ossified cochlea].

A pulsed holmium: YAG-laser (lambda = 2120 nm) was used to reopen the basal turn of artificially obliterated human cochleas in freshly dissected cadavers for intracochlear insertion of the stimulation electrode of a cochlear implant under simulated surgical conditions. Laser energy was transmitted through a 400 microns nylon fibre via the opened facial recess directly to the round window niche. At an energy level of 500 mJ/2.5 microseconds pulse, a repetition rate of 2 Hz, and an exposure time of 20-30 s, the photo-ablative mechanism of laser-bone interaction, which has only a limited thermal component, led to recanalisation of the basal turn of the cochlea in a length of 8-10 mm without damaging the surrounding structures. Light microscopic changes in the cochlea were evaluated following laser recanalisation. The artificial bony occlusion and the recanalised basal turn of the cochlea were visualised by means of computed tomography and histological thin section technique.

Cochlea↗

PubMed1981

Enkephalin-like immunoreactivity of olivocochlear nerve fibers in cochlea of guinea pig and cat.

The distribution of enkephalin-like immunoreactivity in the cochlea of the guinea pig and cat was studied. Indirect immunofluorescence immunohistochemistry using antisera generated against a methionine enkephalin-bovine thyroglobulin conjugate was applied to surface preparations of the organ of Corti and cryostat sections of the whole of the cochlea. In the cochlear osseous spiral lamina, immunofluorescence was localized to unmyelinated fibers of the intraganglionic spiral bundle. In the organ of Corti, immunofluorescence was localized to a small number of fibers at inner hair cells, the inner spiral bundle, and tunnel spiral bundle, to tunnel crossing fibers at the level of the tunnel floor, to an occasional spiral outer fiber, and to the synaptic region of outer hair cells in the three rows of the basal turn of the cochlea. Less immunofluorescence was found in this region as one progressed towards the apex, with none seen at the apex. At the most apical region the inner spiral bundle became patchy and the tunnel spiral bundle developed arcades. There was no immunofluorescence found in spiral ganglion cells, in auditory nerve fibers, or in the hair cells of the organ of Corti. The findings were the same in cat as in guinea pig, the latter being studied in more detail. It was concluded that efferent, olivocochlear neurons of the cochlea, synapsing predominantly with primary auditory nerve fibers from the inner sensory cells or with the sensory cells, contain enkephalin-like immunoreactivity. Also, the findings indicate that endings of olivocochlear neurons that synapse predominantly with outer hair cells contain enkephalin-like immunoreactivity. It has previously been shown that olivocochlear neurons are likely to be cholinergic.

Animals↗

PubMed2003

Steroidogenic enzyme expression in the rat cochlea.

OBJECTIVE: Steroid hormones, and particularly mineralocorticoids, are candidates for controlling the homeostasis of endolymph as steroid receptors are widely expressed in the cochlea. In contrast, experiments on adrenalectomized animals have shown that an absence of steroids had little effect on the ionic composition of endolymph and hearing ability. We thus hypothesized that local production of steroids in the inner ear may regulate cochlear fluid exchanges. RESULTS: Using reverse transcription-polymerase chain reaction techniques, we showed that transcripts encoding the P450 side-chain cleavage, the 3beta hydroxysteroid dehydrogenase (3beta HSD) and the 17alpha hydroxylase (P450 C17) were expressed in the lateral wall, organ of Corti and modiolus. The mRNA encoding aldosterone synthase was expressed in the modiolus and lateral wall while the P450 11beta1 hydroxylase was not detected at all in any of these tissues. In situ hybridization experiments on cochlear sections confirmed that the 3beta HSD transcripts were expressed in the spiral ligament and modiolus and possibly in the hair cells of the organ of Corti. However, it was not possible to detect P450 C17 transcripts. Immunohistochemistry performed with an antibody raised against the various 3beta HSD isoforms confirmed the localization found using in situ hybridization. CONCLUSIONS: These results suggest that enzymes of the steroid pathway leading to mineralocorticoids and sex steroid hormones, but not glucocorticoids, may be expressed in the rat cochlea. This work is in line with the recent description of local production of steroid hormones in the brain (neurosteroids), heart and skin. In the cochlea, the local production of mineralo and sex steroids could account for a paracrine role and could induce specific gene expression through steroid receptors or act via a non-genomic mechanism on membrane receptors or ionic exchangers. Experiments aimed at demonstrating enzymatic activities within cochlea tissues are in progress.

3-Hydroxysteroid Dehydrogenases↗

PubMed2004

Transplantation of neural stem cells into the modiolus of mouse cochleae injured by cisplatin.

This study aimed to examine the possibility of restoration of spiral ganglion neurons, which transmit sound stimulation to the brain, by transplantation of fetal neural stem cells (NSCs) into the modiolus of cochleae. Fetal mouse NSCs expressing green fluorescence were injected into the modiolus of cisplatin-treated cochleae of mice. The temporal bones were collected 14 days after transplantation, and provided histological examination. The cell fate of transplants was determined by immunohistochemistry for a neural or glial cell-marker. Histological analysis 2 weeks after transplantation revealed robust survival of transplant-derived cells in the modiolus of the cochlea. NSCs injected in the basal portion of cochleae migrated as far as the apical end of the modiolus Grafted NSCs expressing a neural cell marker were identified, but the majority of grafted NSCs differentiated into glial cells. These findings suggest the possible use of NSCs in cell therapy for restoration of spiral ganglion neurons. However, further treatments are required to increase the number of NSC-derived neurons in the modiolus to realize functional recovery.

Animals↗

PubMed2001

Cochlear function and transgene expression in the guinea pig cochlea, using adenovirus- and adeno-associated virus-directed gene transfer.

Development of a viral vector that can infect hair cells of the cochlea without producing viral-associated ototoxic effects is crucial for utilizing gene replacement therapy as a treatment for certain forms of hereditary deafness. In the present study, cochlear function was monitored using distortion-product otoacoustic emissions (DPOAEs) in guinea pigs that received infusions of either (E1(-), E3(-)) adenovirus, or adeno-associated virus (AAV), directly into the scala tympani. Replication-deficient (E1(-), E3(-)) adenovirus-directed gene transfer, using the cytomegalovirus (CMV) promoter, drove transgene expression to inner hair cells and pillar cells of the cochlea. AAV transduction was tested with several promoters, such as platelet-derived growth factor (PDGF), neuron-specific enolase (NSE), and elongation factor 1alpha (EF-1alpha) promoters; which drove transgene expression to cochlear blood vessels, nerve fibers, and certain spiral limbus cells, respectively. AAV transgene expression was visualized by green fluorescent protein immunostaining. Immunocytochemistry to heparan sulfate confirmed the absence of proteoglycans in guinea pig hair cells, indicating that the receptor for AAV was not present on these cells. However, the heparan sulfate proteoglycan expression pattern mimicked the AAV transduction pattern. An overall finding was that cochlear function was not altered throughout the infection period using AAV titers as high as 5 x 10(8) IP/infused cochlea. In contrast, cochlear function was severely compromised by 8 days postinfection with adenoviral titers of 5 x 10(8) PFU/infused cochlea, and outer hair cells were eliminated. Thus, cochlear hair cells are amenable to in vivo gene transfer using a replication-deficient (E1(-), E3(-)) adenovirus. However, replication-defective or gutted adenovirus vectors must be employed to overcome the ototoxic effects of (E1(-), E3(-)) adenovirus vectors.

Adenoviridae↗

PubMed2002

Biophysics of the cochlea - biomechanics and ion channelopathies.

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

Animals↗

PubMed2004

Transplantation of bone marrow stromal cells into the cochlea of chinchillas.

This study aimed to evaluate the potential of bone marrow stromal cells for treatment of inner ear diseases. Autologous marrow cells labeled with Dil were implanted into the inner ear of five gentamicin-treated chinchillas. Histological analysis 3 weeks later revealed robust survival of grafted marrow cells in multiple regions within the cochlea. Marrow cells implanted in the basal turn of the cochlea migrated as far as the apical end or into the spiral ligament of the cochlea. Some grafted cells expressed a neuronal or glial cell marker, indicating their ability to differentiate into neuronal or glial cells. Survival, migrational mobility and differentiation of autologous marrow cells in damaged cochlea suggest their potential as transplants for treatment of various degenerative inner ear diseases.

Animals↗

PubMed2000

Nitric oxide synthase inhibitor reduces the apoptotic change in the cisplatin-treated cochlea of guinea pigs.

Cisplatin is known to cause inner ear damage. The role of nitric oxide (NO) in the cochlea of the guinea pigs after injections of cisplatin or a combination of cisplatin and NO synthase (NOS) inhibitor [N(G)-nitro-L-arginine methyl ester (L-NAME)] i.p. was examined by means of immunohistochemistry. Three days after injection, the cochleas were examined immunohistochemically for single-stranded DNA (ssDNA). We found that ssDNA was expressed in the stria vascularis and spiral ganglion cells of the cisplatin-treated cochlea. In the L-NAME/cisplatin-treated cochlea, the number of cells that exhibited positive staining for ssDNA was markedly reduced. High NO levels lead to inner ear dysfunction under pathological conditions. Our results indicate that NO mediates the ototoxicity of cisplatin.

Animals↗

PubMed2001

Expression of p75NTR and its associated protein NADE in the rat cochlea.

OBJECTIVES/HYPOTHESIS: To investigate the expression of the low-affinity neurotrophin receptor p75 (p75NTR) and its associated protein NADE in the cochlea of the developing and the adult rat. Studies such as this one will help to predict the functional role of p75NTR and NADE in cochlear development. STUDY DESIGN: Histochemical evaluation of p75NTR and NADE in the rat cochlea was performed. METHODS: Immunohistochemical analysis was used to localize p75NTR and NADE in the rat cochlea at postnatal (PN) days PN0, PN2, PN4, PN6, PN8, PN10, and PN13 and in the adult. Confocal laser scanning microscopy was used to analyze whole-mount specimens. RESULTS: Immunoreactivity of both p75NTR and NADE was observed in pillar cells. However, these proteins displayed reciprocal expression patterns. Expression of p75NTR was detected at PN0 and PN2, but disappeared after PN4. In contrast, NADE expression was initially detected at PN2 and persisted into adulthood. CONCLUSIONS: The neurotrophin receptor p75NTR and NADE have distinct and independent roles in developing and mature cochlea.

Age Factors↗

PubMed2001

The nucleus double array cochlear implant: a new concept for the obliterated cochlea.

OBJECTIVE: To increase the number of intracochlear electrodes that may be inserted into a totally obliterated cochlea, a special implant has been developed in collaboration with Cochlear Limited. This implant features two separate electrode carriers containing 11 and 10 active electrodes, respectively, as well as a reference electrode located on the receiver-stimulator package. The potential stimulation modes available with this device therefore include monopolar and bipolar stimulation, and stimulation between both arrays. SURGICAL TECHNIQUE: A cochleostomy anterior to the round window provides access to the basal turn (both the scala tympani and the scala vestibuli), and new built connective tissue and bone can be removed until the anterior wall of the basal turn is approached. A second cochleostomy is performed at the second turn caudal of the cochleariform process and 2 mm anterior of the oval window after removal of the incus. New tissue should also be removed if necessary. The two electrode carriers are then placed into the scala tympani of the basal and the scala vestibuli of the second turn, respectively. The remaining surgical procedure is identical with that used for cochlear implantation in patients without obliterated cochleas. PATIENTS: In this clinical study, 10 patients aged 32 to 66 years with an obliterated cochlea each received a double array cochlear implant. All patients had total obliteration of the basal turn either on preoperative imaging or during surgery. Intraoperatively, the second turn was not obliterated in only 4 of 10 patients. Postoperatively, a standard audiologic test battery was used to determine auditory improvement over time. POSTOPERATIVE RESULTS: All patients achieved significantly improved speech understanding when the additional apical electrode array was used, compared with the use of each electrode array independently. No complications occurred. CONCLUSION: In patients with a totally obliterated cochlea, the number of intracochlear electrodes can be increased by use of the Nucleus double array implant. As a result, patients achieve significantly better auditory results.

Adult↗

PubMed2005

Delivery of neurotrophin-3 to the cochlea using alginate beads.

OBJECTIVE: The aim of this study was to design a novel cochlear neurotrophin (NT) delivery system for the rescue of auditory neurons after ototoxicity-induced deafening. BACKGROUND: NT-3 is a trophic growth factor that promotes the survival of the auditory nerve and may have a potential therapeutic role in slowing neuron loss in progressive deafness, especially as an adjunct to the current cochlear implant. Beads made from alginate are biodegradable, slow release substances that can be placed at the round window or inside the cochlea. This study investigated the loading properties, release kinetics, and implantation potential of alginate beads loaded with NT-3. METHODS: Alginate beads were prepared using an ionic gelation technique and postloaded with NT-3. Release of NT-3 was measured using enzyme-linked immunosorbent assay over 5 days. Alginate beads were implanted into deafened guinea pigs for 28 days, after which survival of auditory neurons was assessed. RESULTS: Enzyme-linked immunosorbent assay studies demonstrated a 98% to 99% loading of NT-3 with a slow, partial release over 5 days in Ringer's solution. Furthermore, the addition of heparin to the delivery system modulated NT-3 release to a steadier pattern. Implantation of alginate-heparin beads in guinea pig cochleae produced minimal local tissue reaction. NT-3 loaded beads implanted at both the round window and within the scala tympani of the basal turn provided auditory neurons significant protection from degradation and apoptosis compared with unloaded beads or untreated cochleae. CONCLUSIONS: This study demonstrates alginate beads to be a safe, biodegradable and effective delivery system for NT-3 to the cochlea.

Alginates↗

PubMed2006

Auditory brainstem implant in a child with severely ossified cochlea.

OBJECTIVE: The hearing outcome after implanting a severely ossified cochlea has always been less satisfactory than implanting a patent one. The aim of our study is to present a case where brainstem implantation was successfully performed as an alternative to cochlear implantation in a child with bilateral severe ossification of the cochlea. STUDY DESIGN: Case presentation. This study was conducted at Gruppo Otologico, Rome, Italy, a private referral center for neurotology and skull base surgery. METHODS: The subject of our study was a 12-year-old female child with postmeningitic deafness and bilaterally ossified cochleae. This case is the first brainstem implantation performed at our center with the indication of severe ossification of the cochlea. RESULTS: Successful brainstem implantation of a device was carried out, and the hearing of the patient was restored to the degree that she can freely use the telephone after 8 months of implantation. CONCLUSION: Although more cases are needed before establishing the exact outcome of brainstem implantation in cases of deafness in the presence of severe bilateral cochlear ossification, preliminary results show the superiority of brainstem implants to conventional or even customized cochlear implants.

Auditory Brain Stem Implants↗

PubMed1978

Basilar membrane motion in a spiral-shaped cochlea.

To examine the influence of the spiral coiling of the cochlea upon the motion of the basilar membrane, a mathematical model of the cochlea is constructed. The formulation of the problem leads to Laplace's equation in three dimensions in a curvilinear coordinate system plus corresponding boundary conditions. By basing the choice of the coordinate system upon the form of the helix representing the centerline of the basilar membrane, a relatively simple formulation is obtained. The helix parameters appear only in the Laplacian, not in the boundary conditions. From experimental data the equations of the basilar membrane's centerline are derived for a human cochlea, both in intrinsic form and in regular form. The relative simplicity of the formation permits the tentative conclusion that, in spite of the large curvature near the apex, the spiral shape of the cochlea has only a small influence upon the motion of the basilar membrane.

Basilar Membrane↗

PubMed1986

Loudness summation, masking, and temporal interaction for sensations produced by electric stimulation of two sites in the human cochlea.

Three psychophysical studies were conducted on two multichannel cochlear implant patients. The first study investigated the amount of loudness summation as a function of the spatial separation between two bipolar electrode pairs in the cochlea. Summation was found to increase in an orderly way with the separation between the two electrode pairs. This observation suggested that loudness was related to the distribution of discharge rate of auditory neurons along the cochlea for electric stimulation, and a model of loudness summation formulated on the basis of a functional relationship between loudness and the discharge rate distribution was proposed. The second study investigated the possibility of estimating the discharge rate distribution by means of masking. The amount of masking was found to decrease in an orderly fashion with the spatial separation between the masker and probe electrode pairs. This pattern of masking is consistent with the physiological and modeling observation that the current and neural discharge rate distributions produced by an electrode pair (masker) in the cochlea are approximately bell shaped with gradually decaying borders. The third study investigated the just-discriminable changes in the temporal delay between two interleaving pulse trains delivered, respectively, to two electrode pairs in the cochlea. Discrimination performance was found to decrease with the spatial separation between the two electrode pairs.

Cochlea↗