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PubMed1998

Developmental changes in growth factors released by the embryonic inner ear.

Recent studies have demonstrated a role for neurotrophins in regulating the survival of developing auditory and vestibular neurons. However, the developmental time-course for neurotrophin production and release by inner ear tissues has not been defined. In the present study, neurotrophin-like activity was evaluated from culture medium conditioned by early- or midembryonic stage inner ears. Examination of the proteinaceous properties of conditioned medium revealed a developmental change in growth factor release by the inner ear. Neurotrophin-like molecules were not detected in medium conditioned by early stage otocysts. In contrast, neurotrophin-like bioactivity was detected in medium conditioned by middevelopmental stage inner ears. Western blot analysis revealed that NT-3 was released by the rat inner ear at midstages of inner ear development. ELISA measurements revealed that both NT-3 and BDNF are produced by the middevelopmental stage inner ear, and that NT-3 protein levels are higher than BDNF levels. These results suggest that there are developmental changes in the release of growth factors by the inner ear.

Animals↗
PubMed2006

[Multi-channel cochlear implantation in patients with congenital inner ear malformation accompanied middle ear malformation].

OBJECTIVE: To report the multi-channel cochlear implantation in three patients with congenital inner ear malformation accompanied middle ear malformation, including CI surgery and postoperative outcomes of hearing and speech recovery. METHOD: Multi-channel cochlear implantation surgeries have been performed in three cases with congenital inner ear malformation accompanied middle ear malformation in our hospital from May 1995 to May 2002. The transmastoid approach was performed to the cases with congenital inner ear malformation accompanied middle ear malformation. The postoperative sound field hearing tests were taken to the cases three months after the cochlear implantation. RESULT: Multi-channel cochlear implantation was successfully performed in three cases with congenital inner ear malformation accompanied middle ear malformation. The 27, 28, 32 electrodes were inserted respectively in three cases. The intraoperative "Ozze" occurred in three patients. No severe intraoperative and postoperative complications occurred in three cases. All postoperative hearing thresholds were at 35-40 dBHL. CONCLUSION Multi-channel cochlear implantation could be performed in the cases with congenital inner ear malformation accompanied middle ear malformation through the transmastoid approach. The postoperative outcomes were satisfied.

Child↗
PubMed2001

Roles of fibroblast growth factor 2 during innervation of the avian inner ear.

The importance of individual members of the fibroblast growth factor gene family during innervation of the vertebrate inner ear is not clearly defined. Here we address the role of fibroblast growth factor 2 (FGF-2 or basic FGF) during development of the chicken inner ear. We found that FGF-2 stimulated survival of isolated cochlear and vestibular neurons during distinct phases of inner ear innervation. The potential neurotrophic role of FGF-2 was confirmed by its expression in the corresponding sensory epithelia and the detection of one of its high-affinity receptors in inner ear neurons. Finally, we have analysed the potential of the amplicon system based on defective herpes simplex virus type 1 (HSV-1) vectors to express FGF-2 in cochlear neurons. Overexpression of FGF-2 in cochlear neurons resulted in neuronal differentiation demonstrating the presence of biologically active growth factor. This study underlines the potential of FGF-2 to control innervation and development of sensory epithelia in the avian inner ear. Furthermore, amplicon vectors may provide a useful tool to analyse gene function in isolated neurons of the vertebrate inner ear.

Animals↗
PubMed2003

[Computed tomography and magnetic resonance imaging of acquired abnormalities of the inner ear and cerebello-pontine angle].

CT and MRI of acquired abnormalities of the inner ear and cerebello-pontine angle present themselves with very typical findings. The imaging should be adapted to the pathology looked for and either CT or MRI should be used alone or in combination. CT, especially high resolution CT (HRCT), provides an excellent bone contrast, while MRI has a much superior soft tissue contrast. Acute inflammatory changes of the inner ear are solely depicted by contrast-enhanced MRI. HRCT excellently depicts osseous changes of the inner ear and cerebellopontine angle such as chronic ossifying labyrinthitis occurring after acute labyrinthitis, otosclerotic or traumatic changes. Tumorous changes not yielding to bony changes are best delineated by MRI. Posttraumatic hemorrhage and chronic fibrotic changes within the labyrinth are depicted by MRI, only. In conclusion HRCT and MRI are excellent methods to delineate acquired abnormalities of the inner ear and cerebello-pontine angle. HRCT best depicts osseous changes while MRI best depicts soft tissue changes. HRCT and MRI are not concurrent methods but should better be used as complementary methods for imaging acquired abnormalities of inner ear and cerebellopontine angle.

Cerebellar Neoplasms↗
PubMedDate not supplied

Distribution of HRP in the inner ear after injection into the middle ear cavity.

The distribution patterns of horseradish peroxidase (HRP) reaction products in the inner ears of guinea pigs were studied after injections into the middle ear cavities and perilymphatic and subarachnoid spaces. The normal round window membrane resisted HRP penetration from the middle ear side, but when it became pathological after repeated applications, its permeability increased. HRP deposits were found in the cochlear and vestibular sensory cells and in the lumen of the endolymphatic sac. HRP reaction products were minimal at the cochlear apex even after long survival times, suggesting that perilymph flow, if it exists, is rather weak toward this direction. Whereas the stria vascularis is impermeable to HRP, the vestibular dark cells were accessible; thus, the metabolic activity of the dark cells can be more readily controlled by drug applications through the middle ear cavity. The finding of HRP deposits on the scala vestibuli surface of Reissner's membrane and the absence of HRP in the upper portion of the spiral ligament at the basal turn suggests that the oval window is a secondary route of passage for these particles from the middle ear cavity to the inner ear. In order to determine the route of HRP into the endolymphatic sac from the middle ear cavity or scala tympani, the cochlear and/or vestibular aqueducts were obliterated singly or together. The route of HRP was determined to be the vestibular aqueduct. HRP is believed to enter the sac lumen through Reissner's and saccular membranes and the sac epithelium. Drugs and other large molecular substances instilled in or gaining access to the middle ear cavity may reach the endolymphatic sac causing its functional alteration.

Animals↗
PubMed2006

Eya1 regulates the growth of otic epithelium and interacts with Pax2 during the development of all sensory areas in the inner ear.

Members of the Eyes absent (Eya) gene family are important for auditory system development. While mutations in human EYA4 cause late-onset deafness at the DFNA10 locus, mutations in human EYA1 cause branchio-oto-renal (BOR) syndrome. Inactivation of Eya1 in mice causes an early arrest of the inner ear development at the otocyst stage. To better understand the role of Eya1 in inner ear development, we analyzed the cellular and molecular basis of the early defect observed in the Eya1 mutant embryos. We report here that Eya1-/- otic epithelium shows reduced cell proliferation from E8.5 and increased cell apoptosis from E9.0, thus providing insights into the cellular basis of inner ear defect which occurred in the absence of Eya1. Previous studies have suggested that Pax, Eya and Six genes function in a parallel or independent pathway during inner ear development. However, it remains unknown whether Pax genes interact with Eya1 or Six1 during inner ear morphogenesis. To further evaluate whether Pax genes function in the Eya1-Six1 pathway or whether they interact with Eya1 or Six1 during inner ear morphogenesis, we have analyzed the expression pattern of Eya1, Pax2 and Pax8 on adjacent sections of otic epithelium from E8.5 to 9.5 by in situ hybridization and the inner ear gross structures of Pax2, Eya1 and Six1 compound mutants at E17.5 by latex paintfilling. Our data strongly suggest that Pax2 interacts with Eya1 during inner ear morphogenesis, and this interaction is critical for the development of all sensory areas in the inner ear. Furthermore, otic marker analysis in both Eya1-/- and Pax2-/- embryos indicates that Eya1 but not Pax2 regulates the establishment of regional specification of the otic vesicle. Together, these results show that, while Eya1 exerts an early function essential for normal growth and patterning of the otic epithelium, it also functionally synergizes with Pax2 during the morphogenesis of all sensory areas of mammalian inner ear.

Animals↗
PubMed1986

Scanning electron microscopy of the microvascular system in the inner ear.

In the present work, vessels casts in the inner ear of the rat and guinea pig, prepared by casting method using Mercox resin, were subjected to scanning electron microscopic examination and following results were obtained: In adult guinea pig, numerous capillary nets were found in the following parts: stria vascularis, spiral ligament, spiral prominence, Corti's organ, spiral ganglion, plexus cochlearis, semicircular ampulla, saccule, utricle, and endolymphatic sac. These were consistent with functionally and morophologically important areas in the inner ear. In the central side of the area with capillary nets, arterioles were found to run throughout, like a complex coil, and peripheral capillary diameter was found to be unchanged in an experiment in which the injection pressure was altered, thus autoregulation of blood flow into these important areas is assumed. Vessels in the planum semilunatum were found to form a specific loop-shaped route, where secretion and reabsorption of endolymph is thought to occur. After kanamycin injection into the tympanic cavity, stenosis was observed in capillary nets in the cochlear lateral wall. In guinea pigs on the 30th day of fetal life, the main stem of the inner ear vessel had already formed; however, the peripheral capillary nets were as yet immature in form and vessel density was low.

Alprostadil↗
PubMed2004

Analysis of genes from inner ear developmental-stage cDNA subtraction reveals molecular regionalization of the otic capsule.

Although the gross embryology of inner ear development has been documented for several different vertebrate species at a descriptive level, our understanding of the molecular mechanisms involved remains rudimentary. Therefore, we have used cDNA subtraction and normalization procedures to define genes upregulated in the 13.5dpc mouse inner ear, a developmental stage where inner ear morphogenesis and tissue remodeling is active and differentiation of future hair cells is being initiated. We recovered 33 different genes from this subtraction and using gene-specific primers have confirmed the transcriptional upregulation of 26 of these in the 13.5dpc inner ear. Northern analyses were used to investigate splicing differences between the inner ear and the whole embryo at 13.5dpc. Spatial localization of expression was determined through whole-ear in situ hybridization analysis, and selected genes were analyzed in more detail through in situ hybridization of tissue sections. These data illustrate that the genes isolated in this study are expressed in the developing otic capsule and/or neuroepithelium. Furthermore, the expression patterns also reveal molecular heterogeneity in the developing capsule and indicate that for some genes, the chondrogenic otic capsule is composed of distinct domains of gene expression.

Animals↗
PubMed1998

Detection of transcripts for delayed rectifier potassium channels in the Xenopus laevis inner ear.

Reverse transcriptase polymerase chain reaction (RT-PCR) was used to amplify sequences for delayed rectifier potassium (drk) channel transcripts in Xenopus laevis inner ear and brain. We used degenerate primers that spanned a region between the N-terminal cytoplasmic portion and a region located between the S2 and S3 transmembrane domains of the potassium channel protein. When inner ear total RNA or brain mRNA was used as a template for RT-PCR, a unique product of the expected size (approximately 560 bp) was observed as a single band after electrophoresis on agarose gels. The PCR product from reactions using X. laevis genomic DNA as template was similarly sized, indicating a lack of introns in this region. The RT-PCR products from inner ear and brain were isolated, cloned, and sequenced. Sequence analysis showed that the X. laevis inner ear and brain clones were identical. Sequence alignments of the cloned RT-PCR products with posted GenBank sequences established that the drk sequences from X. laevis inner ear and brain share highest identity with larval X. laevis brain, mouse, rat, and human Kv2 sequences. Positive signals were obtained from inner ear and brain mRNA in Northern dot blots hybridized with digoxigenin labeled probes from the inner ear clone. Taken together, results provide evidence for the expression of Kv2 sequences in the X. laevis inner ear and brain.

Amino Acid Sequence↗
PubMed1989

[A case of ischemic disturbance of inner ear].

We reported a 51-year-old male with ischemic disturbance of right inner ear resembling Meniere's disease. The patient had a sudden-onset episode of vertigo, right severe hearing disturbance, nausea, vomiting and gait disturbance. Two days after, he had hypersomnia, vertical gaze palsy, double vision, left Horner's sign, and sensory disturbance of pain and temperature of right half body involving face. Brain MRI disclosed high intensity area in T2-weighted image and proton density in bilateral paramedian thalamo-mesencephalic region and right cerebellum (area of the anterior inferior cerebellar artery). Cerebral angiography showed 90% or more stenosis of the right vertebral artery, 50% stenosis of the left vertebral artery before the posterior inferior cerebellar artery (PICA), and 60% stenosis of distal portion of the basilar artery. Furthermore, stem portion of the posterior cerebral artery, and the right anterior cerebellar artery and the left vertebral artery after the PICA were absent or occluded. Right deafness was evaluated to be Jerger type II, namely disturbance of inner ear. Caloric tests showed no response, and right auditory brainstem response showed no waves. Main cause of this vertigo and right deafness was considered to be disturbance of inner ear due to ischemia of right labyrinthine artery, though this patient was not a typical case of the anterior cerebellar artery syndrome. Ischemic disturbances of inner ear have been reported only in patients with the anterior cerebellar artery syndrome, therefore this patient who had only acute ischemic disturbance of inner ear and did not have disturbance of caudo-lateral portion of the pons was considered to be very rare.

Cerebral Angiography↗
PubMed1995

Microangiopathy of brain, retina, and inner ear.

Microangiopathy of brain, retina, and inner ear is a rare syndrome manifesting as arteriolar occlusions of the brain, retina, and inner ear, with resultant encephalopathy, visual, and hearing loss. Despite exhaustive laboratory examinations in these patients, no evidence of a systemic disease can be found. We treated and followed an adolescent with this disorder who initially presented with a branch retinal artery occlusion. A unique finding in this case was retinal vessel wall hyperfluorescence noted five days prior to retinal infarction. The patient developed recurrent branch artery occlusions, sensorineural hearing loss, and central nervous system infarctions despite anticoagulation and immunosuppressive treatment.

Adult↗
PubMed2005

[Apoptosis and apoptosis-related genes in experimental autoimmune inner ear disease].

OBJECTIVE: To investigate the protein and mRNA expression patterns of apoptosis-related genes, together with evidence of apoptosis, in relation to experimental autoimmune inner ear disease (AIED). METHODS: Male C57BL/6 mice at 4 weeks age (n = 80) were randomly assigned to one of the five group (n = 16). The inbred mice were given a single subcutaneous injection of diluted solution of pertussis and an emulsion containing equal parts of complete Freund adjuvant (CFA) and inner ear antigens (IEAg) extracted form guinea pig. The animals were sacrificed for inner ear examination at a defined time after the immunization (7, 14, 21 or 28 days). An autoimmune inner ear diseases model was established. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (d-UTP) nick end-laying (TUNEL) method. Using immunohistochemical techniques and reverse transcriptase polymerase chain reaction to clarify the profile of Fas, FasL, and bcl-2. RESULTS: Under normal conditions, no TUNEL-positive cell was observed in the cochlea except for a few positive cells in the supporting cells of Corti's organ and macula sacculi. Inner ear antigens administration induced TUNEL-positive reactions in a wide variety of cells such as inner hair cells, supporting cells, stria vascularis and spiral ligament fibrocytes. No positive staining was evident in outer hair cells, spiral ganglion cells and Scarpa's ganglion cells during the whole period. Fas proteins were expressed in a wide range of cells in inner ear. The levels of Fas mRNA were no significant differences between normal and AIED mice. FasL and bcl-2 proteins could be detected in spiral ganglion cells and Scarpa's ganglion cells both in normal and AIED mice. FasL positive cells increased in number in inner ear of AIED mice. bcl-2 positive cells were not detectable in inner hair cells, stria vascularis and spiral ligament both in normal and AIED mice. The mRNA of three kinds of apoptosis-related genes was detectable in the normal and AIED mice. FasL mRNA was expressed at low levels in normal, being maximal at 14 d post inoculation and decreased gradually to steady levels by 2 weeks. The levels of bcl-2 mRNA increased significantly during the period of AIED. CONCLUSION: Apoptosis mediated by Fas/FasL signal system may play a role in the initiation and maintenance of AIED. bcl-2 has a crucial role in the regulation of the process of apoptosis in the inner ear of AIED mice.

Animals↗
PubMed1994

Hair cell regeneration in the inner ear.

Hearing and balance disorders caused by the loss of inner ear hair cells is a common problem encountered in otolaryngology-head and neck surgery. The postembryonic production of hair cells in cold-blooded vertebrates has been known for several decades, and recent studies in the avian inner ear after ototoxic drug and noise damage have demonstrated a remarkable capacity for both anatomic and functional recovery. The regeneration of sensory hair cells has been shown to be integral to this repair process. Current work is focusing on the cellular progenitor source of new hair cells and the trigger mechanism responsible for inducing hair cell regeneration. Preliminary studies suggest that reparative proliferation may also occur in the mammalian inner ear. Work in this field is moving at a rapid pace. The results thus far have yielded optimism that direct stimulation of hair cell production or transplantation of living hair cells may eventually become treatment modalities for the damaged human inner ear. These proposals would have been considered unrealistic less than 10 years ago, but they now have caught the full attention of both clinician and researcher.

Animals↗
PubMed1998

[Cochlear and retrocochlear deafness induced by immunity with different inner ear tissue antigens].

OBJECTIVES: To inquire into whether the different inner ear tissue antigens could cause different kind of hearing loss, and to find out the disorder positions of auditory system. METHODS: The basilar membrane (BM), spiral ligament (SL), and spiral ganglion (SG) of guinea pigs were removed for making antigens, respectively. Then, we used these antigens to immune guinea pigs. The special humour and cellular immune reaction, hearing function, and inner ear histopathological changes were observed. RESULTS: In BM-antigen and SL-antigen immune group, the various degrees of cochlear microphonic potential disturbance, recruitment, and immune pathological inflammation in cochlear duct and stria vascularis were found. In SG-antigen immune group, auditory nerve compound action potential changes were prominent, and the inner ear pathological damage mainly existed in cochlear axis vessels or surround areas, and SG. CONCLUSIONS: It was confirmed that the inner ear antigens come from different part of auditory system, which could cause cochlear or retrocochlear autoimmune disease.

Animals↗
PubMed1985

[Damage to inner ear function caused by the effect of ionizing rays].

In the literature the inner ear is claimed to be resistent to the effects of ionizing irradiation. We therefore studied the inner ear function in a group of 49 patients who had undergone radiotherapy for malignant tumors of the head in which the irradiated field included at least one inner ear. 67 ears had been irradiated, 46 of them showed a sensorineural hearing loss of 10 dB or more. The frequency and the degree of the inner ear damage was correlated with the dosage of the irradiation and with the time elapsed after the end of radiotherapy.

Adult↗
PubMedDate not supplied

A possible embryonic mechanism for the establishment of innervation of inner ear sensory structures.

The objective of this study was to explore the hypothesis (Van De Water, 1976) that differentiating sensory receptors of the inner ear may attract ingrowing neurites of the statoacoustic (VIIIn) ganglion by chemotaxis. Co-cultured embryonic inner ears which shared a single VIIIn ganglion were grown "in vitro" to the equivalent of 20 days gestation and then processed histologically to show both cytodifferentiation of sensory structures and the presence of neural elements. Specimens of both 11- and 12.5-day-old co-cultured otocysts showed that VIIIn ganglion neurites grew into sensory receptors of both(+) with and (-) without ganglion inner ear explants. Fourteen-day-old co-cultured inner ears revealed that only the (+) ganglion inner ear explants received VIIIn ganglion neurites into the sensory areas, and that neurites were not attracted into the (-) ganglion explants. The results were found to support the hypothesis of a limited period of chemotaxis as being a possible mechanism for the establishment of the pattern of innervation of inner ear sensory receptors by its VIIIn ganglion.

Animals↗
PubMedDate not supplied

Elaboration of systemic immunity following inner ear immunization.

The development of systemic humoral and cellular immunity following antigen presentation in the inner ear was compared with that seen following middle ear and peritoneal inoculation routes. Antibody developing against keyhole limpet hemocyanin was measured by a sensitive enzyme-linked immunofiltration assay, and cell-mediated immunity was measured by in vitro lymphocyte blastogenesis. The inner ear and peritoneal routes of antigen presentation resulted in a parallel rise in antibody over a 3-week period. In contrast, the middle ear route resulted in a weak, transient antibody response by 2 weeks. The acquisition of cell-mediated immunity occurred earliest (day 14) in the group receiving antigen intraperitoneally. A significant but smaller proliferative response was also seen in the group receiving antigen via the inner ear route on days 14 and 21. In contrast, the middle ear route failed to result in cell-mediated immunity. These studies indicate that the inner ear is an effective route of antigen processing which results in the acquisition of systemic humoral and cellular immunity. The development of systemic immunity, in turn, has been found to be protective of the inner ear.

Animals↗
PubMed1998

[Discernment of the sensitized inner ear by peripheral immunocompetent lymphocytes].

OBJECTIVE: To understand the role of peripheral immunocompetent lymphocytes during an immune response in the inner ear. METHODS: Sensitized lymphocytes from peripheral blood, neck lymph nodes and spleen from three groups of donor animals (group A was immunized intradermally with KLH and both inner ears were challenged with KLH; group B received only KLH intradermally without an inner ear challenge, and groups C were naive animals) were labelled with 51Cr and injected intravenously into recipients (all of which were immunized intradermally with right inner ears challenged with KLH). Twenty to twenty-four hours later, the temporal bones of recipients were assayed for radioactivity to detect the infiltration of labelled cells. RESULTS: In group A and B, the right temporal bones showed higher radioactivity than the left temporal bones (P < 0.05). The highest labelling was detected in the right temporal bones of group A. The lowest migration of 51Cr-labelled cells to the inner ear was found in group C animals. The highest ratios between right (challenged) and left (unchallenged) were found in group A animals compared with those of group B and group C. The value was significantly higher in group A than in group B and C (P < 0.05). CONCLUSION: The results showed that the inner ear comes under the immunosurveillance of the peripheral circulation in response to antigenic stimulation.

Animals↗