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Virtual reality modelling language: freely available cross-platform visualization technique for 3-D visualization of the inner ear.

This was a study of the use of virtual reality modelling language (VRML) for cross-platform interactive three-dimensional (3-D) visualization of high-resolution magnetic resonance (MR) images of the inner ear in the assessment of cochlear implant candidates. A retrospective case review was made of cochlear implant candidates undergoing pre-operative high-resolution MR studies to determine their suitability for implantation. 3-D visualizations of MR scans of the inner ear structures were created using surface rendering and exported as portable VRML files. Case studies are presented to illustrate different points of interest. VRML reconstructions aided the interpretation of two-dimensional (2-D) source images in a variety of inner ear abnormalities. VRML is an internationally recognized standard for cross-platform 3-D visualization that creates a means of providing the implanting surgeon with a portable 3-D representation of the inner ear, aiding interpretation of the complex cross-sectional anatomy of these structures, and guiding selection of patients for implantation as well as implantation technique. The elucidation of the mechanisms behind inner ear malformations can also be aided by detailed imaging studies of the temporal bone, with VRML reconstructions providing an easily interpreted representation of deformities.

Adolescent↗

An observation on otoacoustic emission and ultrastructure of cochlea in experimental autoimmune inner ear disease.

OBJECTIVE: To acquire the detailed knowledge of immune lesion of inner ear. METHODS: A simultaneous study on physiology and ultrastructure was carried out in guinea pigs immunized with homogenous inner ear antigen. The specific antibody was analysed by a modified immunotransfer electrophoresis method. RESULTS: Three positive bands (with molecular weights of 68.0 kD, 62.7 kD and 60.1 kD) were found in all the sera of immunized animals but not in the control animals. Threshold shift of auditory brainstem response over 10dB HL was found in 42% of secondary system immunized animals and 32% of secondary endolymphatic sac (e.sac) immunized animals. Amplitude of distortion production otoacoustic emission dropped obviously in the above two groups. Transmission electron microscope showed the mitochondria of outer hair cells in the cochlea was impaired in animals with auditory disorder. CONCLUSIONS: The research suggests that the immune reaction against homogenous inner ear antigen results in dysfunction of hydroxycorticosteroid during the early stage.

Animals↗

Cochlear pharmacokinetics with local inner ear drug delivery using a three-dimensional finite-element computer model.

HYPOTHESIS: Cochlear fluid pharmacokinetics can be better represented by three-dimensional (3D) finite-element simulations of drug dispersal. BACKGROUND: Local drug deliveries to the round window membrane are increasingly being used to treat inner ear disorders. Crucial to the development of safe therapies is knowledge of drug distribution in the inner ear with different delivery methods. Computer simulations allow application protocols and drug delivery systems to be evaluated, and may permit animal studies to be extrapolated to the larger cochlea of the human. METHODS: A finite-element 3D model of the cochlea was constructed based on geometric dimensions of the guinea pig cochlea. Drug propagation along and between compartments was described by passive diffusion. To demonstrate the potential value of the model, methylprednisolone distribution in the cochlea was calculated for two clinically relevant application protocols using pharmacokinetic parameters derived from a prior one-dimensional (1D) model. In addition, a simplified geometry was used to compare results from 3D with 1D simulations. RESULTS: For the simplified geometry, calculated concentration profiles with distance were in excellent agreement between the 1D and the 3D models. Different drug delivery strategies produce very different concentration time courses, peak concentrations and basal-apical concentration gradients of drug. In addition, 3D computations demonstrate the existence of substantial gradients across the scalae in the basal turn. CONCLUSION: The 3D model clearly shows the presence of drug gradients across the basal scalae of guinea pigs, demonstrating the necessity of a 3D approach to predict drug movements across and between scalae with larger cross-sectional areas, such as the human, with accuracy. This is the first model to incorporate the volume of the spiral ligament and to calculate diffusion through this structure. Further development of the 3D model will have to incorporate a more accurate geometry of the entire inner ear and incorporate more of the specific processes that contribute to drug removal from the inner ear fluids. Appropriate computer models may assist in both drug and drug delivery system design and can thus accelerate the development of a rationale-based local drug delivery to the inner ear and its successful establishment in clinical practice.

Animals↗

[Cochlear implant in patients with congenital malformation of inner ear].

OBJECTIVE: To study surgical difficulty and key of the cochlear implant in patients with congenital malformation of inner ear. METHODS: The cochlear implantations were performed in our department from Jan. 2001 to Apr. 2003 for 18 patients with the malformation of inner ear. RESULTS: In this series, there were 11 cases of large vestibular aqueduct syndrome (LVAS), 3 cases of Waardenberg syndrome, 3 cases of Mondini malformation, and 1 case of Usher syndrome. All 18 patients accepted the Nucleus 24-channel cochlear implantations, including Nucleus straight electrode in 13 cases but Contour implantation in 5 cases of LVAS. During operations, leakage of perilymph but not cerebrospinal fluid (CSF) from the open of scala tympani occurred in 11 cases of LVAS, however, the electrode was inserted successfully. The abnormalities of round window occurred in one of 3 cases of Waardenberg syndrome and 3 cases of Mondini malformation, respectively. CONCLUSION: The cochlear implant could be conducted successfully for the LVAS, and the postoperative effect was same as the ones for the deafness persons with normal development of inner ear. However, for the patients with Mondini syndrome and common cavity, it is important to accurately assess the extent of abnormalities in the inner ear and accompanied malformation before operation, and to evaluate the full extent of difficulties of the operation in order to minimize the risk of CSF leakage and meningitis.

Adolescent↗

The primary octaval nuclei and inner ear afferent projections in the otophysan Ictalurus punctatus.

Physical coupling between the swimbladder and the inner ear is believed to contribute to the enhanced hearing abilities of otophysans relative to those of teleosts lacking comparable otic specializations. We hypothesized that the auditory circuitry of otophysans might also exhibit derived features [McCormick and Braford, 1988]. As a first test of this hypothesis, we examined the normal anatomy and inner ear inputs of the primary octaval nuclei in the catfish Ictalurus punctatus. From Nissl-stained sections we conclude that Ictalurus, like other teleosts, has five first-order octaval nuclei: the anterior, magnocellular, tangential, descending, and posterior octaval nuclei. The overall projection pattern of the seven inner ear endorgans, determined using the exsanguinated horseradish peroxidase procedure [McCormick and Braford, 1984], is very similar to that hypothesized as primitive for gnathostome fishes. The otolithic endorgans project to dorsal areas of the descending and anterior nuclei, whereas the macula neglecta and cristae of the semicircular canals project more ventrally. Three zones are recognized within the descending nucleus-the dorsomedial, intermediate, and ventral zones. The dorsomedial zone, which is the main terminus of saccular fibers, has specialized morphological features: it extends far dorsally and contacts the medial portion of the cerebellar crest, and it is partitioned into lateral and medial portions by entering facial nerve fibers. The caudal anterior nucleus is likewise partitioned into lateral and medial portions by the facial nerve. Hypotheses addressing these derived features are presented.

Air Sacs↗

Dynamics of inner ear pressure release, measured with a double-barreled micropipette in the guinea pig.

The inner ear fluid pressure was measured in scala media of the guinea pig through one barrel of a double-barreled micropipette after a sudden volume increase or decrease, caused by injection or withdrawal of artificial endolymph through the other barrel. During injection or withdrawal, the inner ear pressure changed in the order of 1-10 cm water, but it returned to its initial value within a few seconds. The time constant for the pressure recovery depended on the flow direction. It was on average 1.1 s after a short overpressure and 2.8 s after underpressure. The obtained results could be fitted with a simple physical model, when it was assumed that inner ear pressure recovery is a non-linear process, governed by a pressure-dependent flow resistance and/or membrane compliance.

Animals↗

Ultrastructural evidence for hair cell regeneration in the mammalian inner ear.

It has long been thought that hair cell loss from the inner ears of mammals is irreversible. This report presents scanning electron micrographs and thin sections of the utricles from the inner ears of guinea pigs that show that, after hair cell loss caused by treatment with the aminoglycoside gentamicin, hair cells reappeared. Four weeks after the end of treatment, a large number of cells with immature hair bundles in multiple stages of development could be identified in the utricle. Thin sections showed that lost type 1 hair cells were replaced by cells with a morphology similar to that of type 2 hair cells. These results indicate an unexpected capacity for hair cell regeneration in vivo in the mature mammalian inner ear.

Animals↗

[Inner ear damage induced by bacteria (Mycobacterium chelonae)].

Mycobacterium chelonae has a pathogenicity for mouse inner ear, resulting in "spinning disease". The mice were subjected to intravenous injection of 1-1.2 x 10(7) organisms of strain ATCC19977 of M. chelonae subspecies abscessus. Morphological changes in the inner ear were investigated together with changes in behavior and auditory brainstem response (ABR). Three days after injection, the threshold of ABR rose in high frequency and the latency of the fifth wave prolonged. The behaviors of the mice such as "grooming" or "sniffing" were suppressed day by day. Fourteen days after injection, 35% of mice showed abnormal behavior, such as "spinning disease". The damage in the cochlear and vestibular sensory cells were observed using scanning electron microscopy and light microscopy. The inner ear showed serous or purulent labyrinthitis after injection. The most specific change found in purulent labyrinthitis was massive abscess of the cochlea with necrosis. Serous labyrinthitis which might have been induced by bacterial toxins was characterized by homogeneous and eosinophilic precipitates and slight cellular infiltrations in the perilymphatic and endolymphatic spaces. In the organ of Corti, the inner and outer hair cell cilia had degenerated and disappeared. In the vestibular end organs, the sensory cilia were fused, lost and sustained ballooning. The cross links and rough nature of the sensory hair membrane had disappeared in the early stage of serous labyrinthitis.

Animals↗

Neurotrophin and Trk neurotrophin receptors in the inner ear of Salmo salar and Salmo trutta.

Neurotrophins (NTs) and their signal transducing Trk receptors play a critical role in the development and maintenance of specific neuronal populations in the nervous system of higher vertebrates. They are responsible for the innervation of the inner ear cochlear and vestibular sensory epithelia. Neurotrophins and Trks are also present in teleosts but their distribution in the inner ear is unknown. Thus, in the present study, we used Western-blot analysis and immunohistochemistry to investigate the expression and cell localization of both NTs and Trk receptors in the inner ear of alevins of Salmo salar and Salmo trutta. Western-blot analysis revealed the occurrence of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not nerve growth factor (NGF), as well as all three Trk receptors, i.e. TrkA, TrkB and TrkC, the estimated molecular weights of which were similar to those expected for mammals. Specific immunoreactivity for neurotrophins was detected mainly in the sensory epithelia. In particular, BDNF immunoreactivity was found in the maculae of the utricle and saccule, whereas NT-3 immunoreactivity was present in the sensory epithelium of the cristae ampullaris. As a rule the sensory epithelia of the inner ear lacked immunoreactivity for Trks, thus excluding possible mechanisms of autocrinia and/or paracrinia. By contrast, overlapping subpopulations of neurons in the statoacoustic ganglion expressed TrkA (about 15%), TrkB (about 65%) and TrkC (about 45%). The present results demonstrate that, as in mammals and birds, the inner ear of teleosts expresses the components of the neurotrophin-Trk system, but their roles remain to be elucidated.

Animals↗

Expression patterns of aquaporins in the inner ear: evidence for concerted actions of multiple types of aquaporins to facilitate water transport in the cochlea.

Water transport between the perilymph and endolymph is important in regulations of volume and osmotic pressure of the inner ear labyrinth. It is now known that expression of water channels (aquaporins or AQPs) in the cell membrane dramatically increases the ability of water to cross epithelial cells. The aims of the current study were to investigate the cellular localization of AQPs by immunolabeling, and to study the developmental expression and relative abundance of various subtypes of AQPs. We report here that AQP3, AQP7 and AQP9 were expressed in the inner ear. Specific subtypes of AQPs were found in discrete regions expressed by both epithelial cells and fibrocytes in cochlear and vestibular organs. Semi-quantitative measurements showed that AQP4 and AQP1 were the two most abundantly expressed AQP subtypes in the inner ear, and their expressions were dramatically upregulated during development. These data showed a highly localized and largely non-overlapping distribution pattern for different subtypes of AQPs in the inner ear, suggesting the existence of regional subtype-specific water transport pathways, and global regulation of water transport in the inner ear may require concerted actions of multiple types of AQPs.

Aging↗

Contribution of bone marrow hematopoietic stem cells to adult mouse inner ear: mesenchymal cells and fibrocytes.

Bone marrow (BM)-derived stem cells have shown plasticity with a capacity to differentiate into a variety of specialized cells. To test the hypothesis that some cells in the inner ear are derived from BM, we transplanted either isolated whole BM cells or clonally expanded hematopoietic stem cells (HSCs) prepared from transgenic mice expressing enhanced green fluorescent protein (EGFP) into irradiated adult mice. Isolated GFP(+) BM cells were also transplanted into conditioned newborn mice derived from pregnant mice injected with busulfan (which ablates HSCs in the newborns). Quantification of GFP(+) cells was performed 3-20 months after transplant. GFP(+) cells were found in the inner ear with all transplant conditions. They were most abundant within the spiral ligament but were also found in other locations normally occupied by fibrocytes and mesenchymal cells. No GFP(+) neurons or hair cells were observed in inner ears of transplanted mice. Dual immunofluorescence assays demonstrated that most of the GFP(+) cells were negative for CD45, a macrophage and hematopoietic cell marker. A portion of the GFP(+) cells in the spiral ligament expressed immunoreactive Na, K-ATPase, or the Na-K-Cl transporter (NKCC), proteins used as markers for specialized ion transport fibrocytes. Phenotypic studies indicated that the GFP(+) cells did not arise from fusion of donor cells with endogenous cells. This study provides the first evidence for the origin of inner ear cells from BM and more specifically from HSCs. The results suggest that mesenchymal cells, including fibrocytes in the adult inner ear, may be derived continuously from HSCs.

Animals↗

The inner ear ultrastructure from the paddlefish (Polyodon spathula) using transmission electron microscopy.

The structure of the hair cells on each sensory macula from the inner ear of the paddlefish (Polyodon spathula) was studied using scanning and transmission electron microscopy, revealing the nucleated cell bodies and peripheral nerve fibres of the saccule utricle and lagena. Examination of the structures within the cell body revealed comparable features with those found in the inner ear hair cells from bony fish species, although in P. spathula the afferent cell body is almost twice the size. This is the first time that the inner ear hair cells from an Acipenseriform fish have been studied using transmission microscopy, thus providing benchmark anatomical information in relation to the cellular morphology of the afferent receptors from a 'healthy' P. spathula ear. Structural information is of assistance in the study of aquatic animal hearing for environmental monitoring purposes, as morphological data can be used to confirm if evidence of raised hearing thresholds from animals exposed to intense anthropogenic noise or other destructive agents (determined using electrophysiological or behavioural techniques) are a direct result of damage to the ultrastructure of the inner ear.

Animals↗

Requirements for FGF3 and FGF10 during inner ear formation.

Members of the fibroblast growth factor (FGF) gene family control formation of the body plan and organogenesis in vertebrates. FGF3 is expressed in the developing hindbrain and has been shown to be involved in inner ear development of different vertebrate species, including zebrafish, Xenopus, chick and mouse. In the mouse, insertion of a neomycin resistance gene into the Fgf3 gene via homologous recombination results in severe developmental defects during differentiation of the otic vesicle. We have addressed the precise roles of FGF3 and other FGF family members during formation of the murine inner ear using both loss- and gain-of-function experiments. We generated a new mutant allele lacking the entire FGF3-coding region but surprisingly found no evidence for severe defects either during inner ear development or in the mature sensory organ, suggesting the functional involvement of other FGF family members during its formation. Ectopic expression of FGF10 in the developing hindbrain of transgenic mice leads to the formation of ectopic vesicles, expressing some otic marker genes and thus indicating a role for FGF10 during otic vesicle formation. Expression analysis of FGF10 during mouse embryogenesis reveals a highly dynamic pattern of expression in the developing hindbrain, partially overlapping with FGF3 expression and coinciding with formation of the inner ear. However, FGF10 mutant mice have been reported to display only mild defects during inner ear differentiation. We thus created double mutant mice for FGF3 and FGF10, which form severely reduced otic vesicles, suggesting redundant roles of these FGFs, acting in combination as neural signals for otic vesicle formation.

Animals↗

Immunohistochemical localization of the Na-K-Cl co-transporter (NKCC1) in the gerbil inner ear.

We mapped the cellular and subcellular distribution of the Na-K-Cl co-transporter (NKCC) in the adult gerbil inner ear by immunostaining with a monoclonal antibody (MAb T4) generated against human colon NKCC. Heavy immunolabeling was seen in the basolateral plasma membrane of marginal cells in the stria vascularis and dark cells in the vestibular system. Subpopulations of fibrocytes in the cochlear spiral ligament and limbus and underlying the vestibular neurosensory epithelium also stained with moderate to strong intensity, apparently along their entire plasmalemma. Because MAb T4 recognizes both the basolateral secretory (NKCC1) and the apical absorptive (NKCC2) isoforms of the co-transporter, we employed reverse transcription and the polymerase chain reaction (RT-PCR) to explore isoform diversity in inner ear tissues. Using NKCC1 and NKCC2 isoform-specific PCR primers based on mouse and human sequences, only transcripts for NKCC1 were detected in the gerbil inner ear. The presence of abundant NKCC1 in the basolateral plasmalemma of strial marginal and vestibular dark cells confirms conclusions drawn from pharmacological and physiological data. The co-expression of NKCC1 and Na,K-ATPase in highly specialized subpopulations of cochlear and vestibular fibrocytes provides further evidence for their role in recycling K+ leaked or effluxed through hair cells into perilymph back to endolymph, as postulated in current models of inner ear ion homeostasis.

Animals↗

Histologic demonstration of glycosaminoglycans in inner ear fluids.

Hyaluronic acid is a glycosaminoglycan (GAG) which has been demonstrated by biochemical and histochemical methods to be present in inner ear fluids and tissues. However, consistent labeling of hyaluronic acid or other GAGs in inner ear fluid compartments in histologic sections has not been previously reported. Staining and characterization of GAGs in the normal inner ear fluids of humans and guinea pigs are described in this report. It was initially observed that alcian blue produces dense staining of the endolymphatic and perilymphatic fluid compartments in celloidin embedded material. Results obtained with alcian blue were subsequently compared to staining obtained with hematoxylin/eosin and periodic acid/Schiff base. Enzyme digestion was also performed with testicular hyaluronidase (bovine and ovine), streptomyces hyaluronidase, chondroitase ABC, and alpha-amylase. Results of the differential staining and enzyme digestion studies suggest that the substances in inner ear fluids that stain with alcian blue are a combination of chondroitin sulfate-4, -5 and/or -6 and hyaluronic acid.

Alcian Blue↗

Inner ear anomalies are frequent but nonobligatory features of the branchio-oto-renal syndrome.

OBJECTIVE: To summarize the syndromic features and evaluate the presence of inner ear anomalies in 35 patients with branchio-oto-renal (BOR) syndrome from 6 families. DESIGN: Retrospective evaluation of magnetic resonance imaging of the temporal bones and clinical features in patients with BOR syndrome. SETTING: Tertiary referral center. PATIENTS: The study population comprised 35 clinically affected patients with BOR syndrome from 6 families. Most of these families were followed for over 25 years. MAIN OUTCOME MEASURES: Twenty-four patients underwent high-resolution, heavily T2-weighted 3-dimensional magnetic resonance imaging of the temporal bones for evaluation of inner ear anomalies. Special attention was paid to the endolymphatic duct and sac. RESULTS: A total of 7 enlarged endolymphatic ducts and sacs (3 bilaterally and 4 unilaterally) and 5 enlarged endolymphatic ducts only (2 bilaterally and 3 unilaterally) were observed. Eight hypoplastic cochleas and 6 hypoplastic labyrinths were seen bilaterally. Seven family members had normal inner ears. CONCLUSION: These findings suggest that inner ear anomalies are frequent but nonobligatory features of BOR syndrome.

Adult↗

Interrelations between the middle and inner ear in otitis media.

This article reviews the importance of the round-window membrane in exposing the labyrinth to or protecting it from the toxic effects of otitis media. Characteristics of the immune system in the human middle ear and middle-ear mechanisms against bacteria are explained. The role of bacteria and bacterial products in inner-ear damage is detailed, and related pathological events are described. The hypothetical role of inflammatory mediators in bacteria-induced inner-ear toxicity is particularly emphasized. Clinical conditions causing these events are detailed, and the most frequently involved microorganisms are mentioned. Finally, round-window membrane macroscopic and microscopic anatomy is discussed, and considerations about the exact role of membrane inflammation--protection versus damage of the inner ear--are expressed.

Bacterial Toxins↗

Fetal respiratory distress causing CNS and inner ear hemorrhage.

Fifty-two consecutive temporal bones of infants who died neonatally, or in utero of natural causes, were studied. Complete autopsies were performed. Twenty-eight infants had a variety of pulmonary disorders which resulted in severe respiratory distress prior to their death. Of these, the majority had bleeding intracranially and into the inner ear. There were five major pathways of central nervous system and subarachnoid hemorrhage involvement of the inner ear: 1) the modiolus, 2) cochlear aqueduct, 3) retrograde via the cochlear vein, 4) episodes of spontaneous bleeding into various compartments of the inner ear, and 4) hemorrhage via the otic capsule. The remaining 24 infants died of other natural causes. Two had CNS bleeding with no extension to the inner ear. We propose that there is a syndrome which consists of 1) neonatal respiratory distress, 2) intracranial hemorrhage, and 3) bleeding into the inner ear--an extension of a subarachnoid or subependymal matrix bleeding diathesis.

Cerebral Hemorrhage↗