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[Inner ear injuries in breath-holding divers].

Five breath-hold divers with inner ear barotrauma due to the diving to 10 meters of depth have been treated at the Department of Otorhinolaryngology, Pula Medical Centre during 1990. Because of eustachian tube dysfunction, a negative middle ear pressure is transmitted into the inner ear over the round and oval window causing a lower hydrostatic pressure of the inner ear fluids and consequent delay in microcirculation of the inner auditory artery. Together with a hypoxia in apnea the oxygen demand is increased and the inner ear neuroepithelium damage is more severe. All treated divers had irreversible sensorineural hearing loss of the attacked ear on frequency range higher than 2000 Hz to 70-80 dB.

Adult↗

Identification of genes expressed in the Xenopus inner ear.

Recent studies indicate that hearing loss in humans has strong hereditary components associated with expression of specific genes in the auditory apparatus of the inner ear. However, the inner ear poses challenges for molecular research because the amount of tissue that can be isolated is limited, and extraction procedures yield small quantities of RNA and protein. To begin to identity genes essential for auditory function, we synthesized a cDNA library using an RT-PCR protocol and total RNA isolated from eight Xenopus laevis inner ears. Sequence analysis of randomly selected clones demonstrated expression of both identified (calmodulin, SNARE protein, syndecan-2) and unidentified genes, and confirmed synthesis of full length transcripts. Confocal and scanning electron microscopy (SEM) were used to examine the structure of inner ear organs that serve as auditory receptors in amphibians: the sacculus, the amphibian papilla and the basilar papilla. SEM images illustrate the heterogeneity of bundle morphology and demonstrate the continuous appearance of stereociliary bundles in the X. laevis amphibian papilla during larval development and adult life. Investigations of gene expression in Xenopus auditory organs using clones recovered from inner ear cDNA libraries should provide insight regarding the molecular basis of hearing.

Animals↗

Epithelial autonomy in the development of the inner ear of a bird embryo.

The epithelium lining the inner ear contains a large number of differentiated cell types, arranged in precise patterns. Once the otocyst has closed, do the cells differentiate according to mechanisms intrinsic to the epithelium or are they dependent on external influences? In particular, are they governed by signals from the surrounding periotic mesenchyme? And is the closed structure of the inner ear or the otocyst fluid that it contains important for pattern formation and differentiation as it is for adult function? We have examined these questions by two types of grafting experiment. In the first, early (E3, stage 17-18, or E2, stage 13-14) undifferentiated quail otocysts were stripped of their mesenchyme and grafted into the wing buds of chick embryos. Although surrounded by a foreign mesenchyme the otic epithelium differentiated into the standard inner ear cell types. The gross morphology was abnormal, and the sensory hair cells were grouped into a few large patches instead of the usual eight smaller patches; locally, however, the spatial relationships between the differentiated cell types appeared normal. In the second experiment, open fragments of early undifferentiated otocyst (with some adhering mesenchyme) were grafted onto the surface of a limb bud. In this exposed in vivo situation, where the apical surface of the epithelium is bathed by amniotic fluid instead of otocyst fluid, differentiation proceeds normally also. Thus differentiation of inner ear epithelium at these stages does not require any specific influence from otic mesenchyme and proceeds independently of whether the otocyst is open or closed. Such epithelial autonomy creates special opportunities for in vitro analysis.

Animals↗

The lateral-line and inner-ear afferents in larval and adult urodeles.

The inner-ear and lateral-line afferents were studied in members of almost all urodele families and in two primitive representatives of anurans and gymnophionans by means of transganglionically transported horseradish peroxidase. The lateral-line projection patterns are, when present, identical in all urodeles and gymnophionans. This is in agreement with the presence of ampullary organs in all urodeles and gymnophionans which possess a lateral-line neuromast system. In contrast, even the most primitive anurans lack both ampullary organs and the dorsal projection of afferents from these organs. In urodeles the inner-ear afferents are found to enter the rhombencephalon via the octaval nerve and bifurcate in the neuropil lateral to the nucleus magnocellularis into a short ascending and a longer descending subpial fascicle. Fibers of the ascending fascicle reach the tip of the lateral recess and terminate in the eminentia granularis. Collaterals are confined to the ipsilateral lobulus lateralis and end presumably as mossy fibers. The descending fascicle ends at the obex level with only a few fibers reaching the second spinal segment. Besides extensive fiber supply to the cells of the ipsilateral ventral-zone column, collaterals are found to reach the reticular formation, nucleus cerebelli, nucleus fasciculus solitarius, intermediate nucleus and several motor nuclei. Differences in the octaval projection among urodele families are limited to variation in its size relative to that of the lateral-line projection. Only species that develop without free-living larvae differ markedly with respect to the absence of lateral-line projections and, presumably, the lateral-line nuclei of the alar plate that exists in larvae. Almost all urodeles that possess a lateral-line system as larvae retain a complete lateral-line system, including neuromasts and ampullary organs, after metamorphosis. Only Salamandra and Chioglossa lose most of their lateral-line afferents and presumably all lateral-line organs around metamorphosis. The octavolateralis projections in urodeles are found to be strikingly similar to those in lampreys, sharks, sturgeons, and, especially, gymnophionans. This points to a great conservatism of this pattern, at least among anamniotic vertebrates. However, even primitive anurans such as Ascaphus differ markedly from these patterns in that they show no ampullary organs or dorsal lateral-line projection but a dorsal projection of the inner ear. Outgroup comparison with other anamniotic vertebrates indicates that the pattern in anurans is derived from the more generalized lateral-line and inner-ear projection pattern as represented in many urodeles and gymno

Amphibians↗

Transcription factors and the control of inner ear development.

The development of the cells and tissues of the inner ear is controlled in part by the sequential expression of transcription factors, and recent studies have begun to define the roles played by such factors in morphogenesis of the labyrinth. A number of transcription factors have been shown to be expressed during inner ear development. Moreover, several genetic disorders of inner ear development in human and mouse have recently been identified as being caused by mutations of genes controlling transcription factors. In addition, the targeted mutation of several transcription factor genes influence the development of specific inner ear cell types, and suggest a critical role for these factors in controlling inner ear cell lineages. In particular, the POU-domain transcription factors are widely expressed in the developing ear. Gene deletion studies suggest that the Class IV POU-domain transcription factor Brn-3.1 is required for the development of auditory and vestibular hair cells, while Brn-3.0 is necessary for appropriate migration and numbers of spiral ganglion neurons.

Journal Article↗

Immunopathology of the inner ear: an update.

We have reviewed the events of an inner-ear immune response. The perilymph contains antibody, presumably derived from the systemic circulation and CSF, which would allow for neutralization and help with opsonization and complement fixation. The endolymphatic sac contains immunocompetent cells capable of processing and presenting viral or bacterial antigen, potentiating the immune response, attacking the invaders directly or attacking infected cells, and developing immunoglobulin responses in situ. The early release of mediators such as IL-2 likely emanate from the endolymphatic sac and result in potentiation and regulation of the response and may assist in changes in the SMV, including expression of ICAM-1, which aid in the egress of immune cells from the systemic circulation. PMNs arrive first, followed by T cells and B cells, with secretion of specific antibody a relatively late event. Concomitant with the increase in cellular constituents is the formation of a dense extracellular matrix. The inner ear appears to have remarkable difficulty in clearing this matrix, ultimately resulting in ossification. The immune response is unfortunately deleterious to the inner ear, resulting in degeneration of the organ of Corti, stria vascularis, and spiral ganglion. Hearing loss is consistently seen following sterile and virally induced labyrinthitis. The inner ear also appears to be a target for autoimmune disease. While inner-ear damage has been described as part of non-organ-specific autoimmune disease, specific disease against the hearing apparatus is also likely. Experimental paradigms have allowed alterations of both the afferent and efferent limbs of this response; ultimately, with the hope that we can alter the course of the response and the subsequent damage in patients.

Animals↗

Surgery of the inner ear with hearing preservation: serial histological changes.

OBJECTIVES/HYPOTHESIS: Surgery of the inner ear can result in hearing preservation under certain conditions, but the mechanisms responsible for hearing preservation or loss are not well understood. The specific aim of the study is to examine histological sections obtained at different time intervals after varying degrees of surgical entry into the inner ear, to understand how the cochlea is protected. The hypothesis is that internal partitioning occurs. STUDY DESIGN: Histologic examination of guinea pig inner ears by light microscopy. METHODS: Guinea pigs underwent lateral semicircular canal transection and plugging, ampullectomy, or vestibulotomy, and tone-burst auditory brainstem response thresholds at 2, 8, and 24 kHz were measured at intervals before and after surgery. Animals were killed after 1, 3, 7, or 21 or more days, and temporal bones were examined histologically. RESULTS: The histological response to surgical trauma consists of fibrosis and varying amounts of inflammation near the site of surgical entry. Cochlear hair cells are nearly always preserved, even when hearing loss occurs. Extension of the inflammatory response to the cochlea is associated with greater degrees of hearing loss. CONCLUSION: The guinea pig inner ear is capable of withstanding surgical trauma to the semicircular canals and vestibule without complete loss of cochlear function. Fibrosis creates an effective partition between the site of surgical entry and the rest of the inner ear. Cochlear preservation might be enhanced if the inflammatory response can be contained.

Animals↗

Simulation of application strategies for local drug delivery to the inner ear.

Local, rather than systemic, drug delivery to the inner ear is becoming more widely used to treat inner ear disorders. While many substances are undergoing preclinical and clinical studies, it is equally important to develop appropriate drug delivery systems. Pharmacokinetic studies are technically demanding in animals and almost impossible in humans. Computer simulations have helped establish the basic principles of drug distribution in the inner ear. The distribution of methylprednisolone in the guinea pig cochlea has been simulated for different drug delivery systems based on kinetic parameters established in prior studies. Results were compared for different rates of drug clearance from the middle ear. Absolute and relative drug levels in the perilymph were highly dependent on how long the drug remained in the middle ear. For a brief (30 min) application, the basal to apical drug gradient was higher than for longer delivery times. These findings show that controlling middle ear drug clearance is of critical importance.

Animals↗

Automatic measurement of the labyrinth using image registration and a deformable inner ear atlas.

RATIONALE AND OBJECTIVES: This article presents a new method for measuring the shape of the cochlea, vestibule, semi-circular canals, and internal auditory canal using image registration and a deformable inner ear atlas. MATERIALS AND METHODS: Computed tomography images of the inner ear are analyzed by placing them into a common orientation and then registering a digital atlas of the inner ear to the data set. The atlas is deformed from its original shape to match the shape of the inner ear in the computed tomography data set using inverse consistent elastic image registration. This process produces an individualized inner ear atlas containing subject-specific measurements and segmentations of the inner ear anatomy in the target computed tomography data set. The shape measurements include the volume and length of the cochlea, vestibule, semi-circular canals, and internal auditory canal; and the angles between the semi-circular canals. RESULTS: A simulated population of inner ear shapes were generated based on the shape of a real population of inner ear shapes and were used to characterize the measurement error of this method. The deformable atlas was used to measure the shape of the left and right inner ear of six individuals. CONCLUSION: Measurement error for 15 of the 24 measurements of our simulated population had an average error of less than 1% and only one measurement had an average error greater than 2.54%. The deformable human inner ear atlas shows promise as a new method for automatically measuring the shape of the labyrinth.

Adult↗

Inner ear volumetric measurements using high-resolution 3D T2-weighted fast spin-echo MR imaging: initial experience in healthy subjects.

BACKGROUND AND PURPOSE: Adult size is achieved in the inner ear labyrinth by approximately 25 weeks' gestation, and minimal variability in age, sex, side, and race is found after birth. In this study, we opted to determine the reproducibility of inner ear volumetric measurements generated from high-resolution heavily T2-weighted 3D fast spin-echo MR images. METHODS: The temporal bones of 23 volunteers were imaged using a heavily T2-weighted 3D fast spin-echo MR imaging technique. The images were assessed by a neuroradiologist for the presence of inner ear configurational anomalies and, most important, for complete coverage of the inner ear labyrinth. Subsequently, the volume of the fluid in the inner ear was determined by two observers using a semiautomated segmentation algorithm. The mean, SD, range, and coefficient of variation of fluid volume in the inner ear were calculated. Age-, sex-, and side-related differences in the inner ear volumetric measurements were evaluated using analysis of variance. Interrater consistency in the inner ear volumetric measurements was evaluated by comparing the calculated coefficients of reliability. RESULTS: Volumetric measurements were available from 46 inner ears in 23 volunteers. The mean volume was 227.8 mm3 (SD, 24.4 mm3), and the coefficient of variation was 10.7%. No age-, sex-, or side-related differences in the inner ear volumetric measurements were found (F ratios were 4.33, 5.04, and 0.26, respectively). Interrater consistency, as assessed by the coefficient of reliability, was 5.3%. CONCLUSION: Reproducible volumetric measurements of the inner ear labyrinth can be obtained by applying a semiautomated segmentation algorithm to a heavily T2-weighted 3D fast spin-echo MR imaging data set. These volumetric measurements may help identify patients with congenital sensorineural hearing loss and normal inner ear configuration.

Adult↗

Three-dimensional imaging of the inner ear by volume-rendered reconstructions of magnetic resonance data.

OBJECTIVE: To evaluate 3-dimensional inner ear visualization by volume rendering of high-resolution magnetic resonance data in patients with clinically suspected inner ear abnormality. DESIGN: Prospective comparative study of different postprocessing techniques, based on blinded film readings. SETTING: Tertiary referral hospital. SUBJECTS: Fifty patients (17 females and 33 males) aged 1 to 77 years (average age, 42 years) with sensorineural hearing loss, vertigo, and/or tinnitus. INTERVENTION: Postprocessing of magnetic resonance data to inner ear reconstructions by the use of volume rendering as well as maximum-intensity projection; caloric testing by electronystagmography. MAIN OUTCOME MEASURES: Film was read blindly by 4 radiologists using a 5-point parameter scale for image quality and diagnostic value. The assessibility of inner ear subsegments was evaluated. The specificity of volume-rendered reconstructions for detecting semicircular canal obliterations was assessed in a subgroup of 9 patients by caloric testing. The time required for data postprocessing as well as film reading was recorded by means of a stopwatch. RESULTS: Volume-rendered inner ear reconstructions were superior in image quality (P<.001), diagnostic value (P<.001), subsegment inner ear assessment (P<.01 to P<.001), and film reading time (P<.001) compared with maximum-intensity projections. The data postprocessing time was comparable for both techniques. Caloric weakness was noted in all patients assessed by electronystagmography. CONCLUSION: Volume rendering is the postprocessing technique of choice for 3-dimensional inner ear visualization, performing better than maximum-intensity projections with respect to various parameters.

Adolescent↗

Origin of the vertebrate inner ear: evolution and induction of the otic placode.

The vertebrate inner ear forms a highly complex sensory structure responsible for the detection of sound and balance. Some new aspects on the evolutionary and developmental origin of the inner ear are summarised here. Recent molecular data have challenged the longstanding view that special sense organs such as the inner ear have evolved with the appearance of vertebrates. In addition, it has remained unclear whether the ear originally arose through a modification of the amphibian mechanosensory lateral line system or whether both evolved independently. A comparison of the developmental mechanisms giving rise to both sensory systems in different species should help to clarify some of these controversies. During embryonic development, the inner ear arises from a simple epithelium adjacent to the hindbrain, the otic placode, that is specified through inductive interactions with surrounding tissues. This review summarises the embryological evidence showing that the induction of the otic placode is a multistep process which requires sequential interaction of different tissues with the future otic ectoderm and the recent progress that has been made to identify some of the molecular players involved. Finally, the hypothesis is discussed that induction of all sensory placodes initially shares a common molecular pathway, which may have been responsible to generate an 'ancestral placode' during evolution.

Animals↗

[Immunology of the inner ear].

Immunological mechanisms may play an important role in the pathogenesis of such inner ear disorders as sudden or rapidly progressive sensorineural hearing loss. As the human inner ear remains unaccessible for immunological studies in clinical practice, the pathogenesis of a possible immune-mediated disease affecting the inner ear still is unclear. Most immunological studies are performed in animal models or concentrate on clinical laboratory tests with patients' blood samples. Experimental data from animal models has shown that the inner ear is capable of immunoprotection by recognizing and processing antigen. Its answer to a local antigen challenge is an immune response with immunoglobulin synthesis. Clinical data from systemic disease have revealed that immune-mediated processes are involved in the pathogenesis of vestibulocochlear disorders. However, a specific testing system for identifying possible antigens or antibodies involved in inner ear diseases is still not available.

Animals↗

Electron microscopical evidence for common inner ear and lateral line efferents in urodeles.

The efferents of the lateral line system and the inner ear were examined in urodeles using retrograde labelling with horseradish peroxidase (HRP). The Golgi-like filling thus achieved allowed tracing of the axons of efferent cells from one inner ear to the other and from the lateral line nerves into both inner ears. Electron microscopic examination of the inner ear revealed HRP label only in vesicle filled terminals on hair cells traditionally considered as efferent synapses. These data confirm earlier claims of common bilateral inner ear and lateral line efferents. In addition, the efferent nature of retrogradely labelled rhombencephalic cells is proven by their continuity with ultrastructurally identified efferent synapses in the inner ear.

Animals↗

Development of the inner ear efferent system across vertebrate species.

Inner ear efferent neurons are part of a descending centrifugal pathway from the hindbrain known across vertebrates as the octavolateralis efferent system. This centrifugal pathway terminates on either sensory hair cells or eighth nerve ganglion cells. Most studies of efferent development have used either avian or mammalian models. Recent studies suggest that prevailing notions of the development of efferent innervation need to be revised. In birds, efferents reside in a single, diffuse nucleus, but segregate according to vestibular or cochlear projections. In mammals, the auditory and vestibular efferents are completely separate. Cochlear efferents can be divided into at least two distinct, descending medial and lateral pathways. During development, inner ear efferents appear to be a specific motor neuron phenotype, but unlike motor neurons have contralateral projections, innervate sensory targets, and, at least in mammals, also express noncholinergic neurotransmitters. Contrary to prevailing views, newer data suggest that medial efferent neurons mature early, are mostly, if not exclusively, cholinergic, and project transiently to the inner hair cell region of the cochlea before making final synapses on outer hair cells. On the other hand, lateral efferent neurons mature later, are neurochemically heterogeneous, and project mostly, but not exclusively to the inner hair cell region. The early efferent innervation to the ear may serve an important role in the maturation of afferent responses. This review summarizes recent data on the neurogenesis, pathfinding, target selection, innervation, and onset of neurotransmitter expression in cholinergic efferent neurons.

Animals↗

[The role of MRI in suspected inner ear malformations].

PURPOSE: This is a prospective analysis of the value of MRI in suspected inner ear malformations. MATERIALS AND METHODS: In 50 patients (43 children and young adults, 7 adults) with suspected inner ear malformation MRI (1.5 T) was performed. In addition, 42 of these patients underwent CT. For the analysis of the inner ear structures, the constructive interference in steady state (CISS) sequence with 0.7 mm slice thickness was used. Functional tests revealed a sensorineural hearing loss or deafness in 82 temporal bones (TB) and a combined hearing loss in 4 TB. The hearing loss was unilateral in 14 patients. MRI and CT findings were compared. RESULTS: Imaging findings were normal in 58 TB. The pathological findings included inner ear malformations (35 TB), inflammatory changes (4 TB), partial obliteration of labyrinth (2 TB) and congenital aural atresia (1 TB). An isolated absence of the cochlear nerve (1 TB) could only be found by MRI. In the remaining cases, an inner ear malformation was diagnosed by MRI and CT with the same confidence but MRI was superior in displaying the fine details. CONCLUSIONS: MRI will become the method of choice in the diagnosis of inner ear malformations.

Adolescent↗

Recurrent inner ear decompression sickness associated with a patent foramen ovale.

Isolated inner ear injuries occurring during shallow scuba dives are an uncommon manifestation of decompression sickness in recreational divers. We describe a patient who presented with the typical symptoms of inner ear involvement after 2 independent dives within the decompression limits. The diver reported symptoms of unilateral (right-sided) hearing loss, tinnitus, and vertigo after dives to 35 and 50 m. After treatment with hyperbaric oxygen, his symptoms completely resolved. To confirm the hypothesis of inner ear decompression sickness (IEDCS), we examined the patient for a right-to-left shunt by cranial Doppler ultrasound and found a patent foramen ovale. The existence of a patent foramen ovale is suspected to be a risk factor for developing neurological symptoms of decompression sickness. There was no evidence of any other risk factors, so we suggest that the relevant right-to-left shunt in our patient may have been the predisposing factor that caused the inner ear symptoms during his scuba dive.

Adult↗

Immunology of the inner ear: evidence of local antibody production.

Previously we reported the capacity of the inner ear to respond immunologically by demonstrating a rise in perilymph antigen-specific antibody following inner ear sensitization. This rise in perilymph antibody was either the result of increased vascular permeability to serum immunoglobulins or the result of local antibody production. In order to determine if the inner ear was the source of antibody, a serum reference was established by systemically immunizing animals to bovine serum albumin (BSA). With anti-BSA as a serum marker during inner ear immunization with keyhole limpet hemocyanin (KLH), we were able to demonstrate an increase in anti-KLH perilymph antibody levels without a corresponding increase in anti-BSA levels. This suggested that increased vascular permeability was not responsible for the increased perilymph levels and that local production of antibody had occurred within the inner ear. The response was independent of the cerebrospinal fluid.

Animals↗