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The braincase anatomy of the Pennsylvanian diadectomorphLimnoscelis dynatisis described in detail, based upon high-resolution X-ray microcomputed tomography. Both supraoccipitals and most of the prootics and opisthotics are preserved. The known portions of the left prootic, opisthotic, and supraoccipital enclose complete sections of the endosseous labyrinth, including the anterior, posterior, and lateral semicircular canals, the vestibule, the cochlear recess, and the canal for the endolymphatic duct. The fossa subarcuata is visible anteromedial to the anterior semicircular canal. The presumed endolymphatic fossae occur in the dorsal wall of the posteromedial portion of the supraoccipital. Both the fossa subarcuata and the fossa endolymphatica lie in the cerebellar portion of the cranial cavity. In order to investigate the phylogenetic position ofL. dynatiswe used a recently published data matrix, including characters of the braincase, and subjected it to maximum parsimony analyses under a variety of character weighting schemes and to a Bayesian analysis.Limnoscelis dynatisemerges as sister taxon toL. paludis, and both species form the sister group to remaining diadectomorphs. Synapsids and diadectomorphs are resolved as sister clades in ∼90% of all the most parsimonious trees from the unweighted analysis, in the single trees from both the reweighted and the implied weights analyses, as well in the Bayesian tree.

Background: The etiology of Meniere's disease (MD) and endolymphatic hydrops believed to underlie its symptoms remain unknown. One reason may be the exceptional complexity of the human inner ear, its vulnerability, and surrounding hard bone. The vestibular organ contains an endolymphatic duct system (EDS) bridging the different fluid reservoirs. It may be essential for monitoring hydraulic equilibrium, and a dysregulation may result in distension of the fluid spaces or endolymphatic hydrops.Material and Methods: We studied the EDS using high-resolution synchrotron phase contrast non-invasive imaging (SR-PCI), and micro-computed tomography (micro-CT). Ten fresh human temporal bones underwent SR-PCI. One bone underwent micro-CT after fixation and staining with Lugol's iodine solution (I2KI) to increase tissue resolution. Data were processed using volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and tissue segmentation.Results: Combined imaging techniques with segmentation and tissue modeling demonstrated the 3D anatomy of the human saccule, utricle, endolymphatic duct, and sac together with connecting pathways. The utricular duct (UD) and utriculo-endolymphatic valve (UEV or Bast's valve) were demonstrated three-dimensionally for the first time. The reunion duct was displayed with micro-CT. It may serve as a safety valve to maintain cochlear endolymph homeostasis under certain conditions.Discussion: The thin reunion duct seems to play a minor role in the exchange of endolymph between the cochlea and vestibule under normal conditions. The saccule wall appears highly flexible, which may explain occult hydrops occasionally preceding symptoms in MD on magnetic resonance imaging (MRI). The design of the UEV and connecting ducts suggests that there is a reciprocal exchange of fluid among the utricle, semicircular canals, and the EDS. Based on the anatomic framework and previous experimental data, we speculate that precipitous vestibular symptoms in MD arise from a sudden increase in endolymph pressure caused by an uncontrolled endolymphatic sac secretion. A rapid rise in UD pressure, mediated along the fairly wide UEV, may underlie the acute vertigo attack, refuting the rupture/K+-intoxication theory.

Background: Reports vary on the incidence of vestibular dysfunction and dizziness in patients following cochlear implantation (CI). Disequilibrium may be caused by surgery at the cochlear base, leading to functional disturbances of the vestibular receptors and endolymphatic duct system (EDS) which are located nearby. Here, we analyzed the three-dimensional (3D) anatomy of this region, aiming to optimize surgical approaches to limit damage to the vestibular organ.Material and Methods: A total of 22 fresh-frozen human temporal bones underwent synchrotron radiation phase-contrast imaging (SR-PCI). One temporal bone underwent micro-computed tomography (micro-CT) after fixation and staining with Lugol's iodine solution (I2KI) to increase tissue contrast. We used volume-rendering software to create 3D reconstructions and tissue segmentation that allowed precise assessment of anatomical relationships and topography. Macerated human ears belonging to the Uppsala collection were also used. Drilling and insertion of CI electrodes was performed with metric analyses of different trajectories.Results and Conclusions: SR-PCI and micro-CT imaging demonstrated the complex 3D anatomy of the basal region of the human cochlea, vestibular apparatus, and EDS. Drilling of a cochleostomy may disturb vestibular organ function by injuring the endolymphatic space and disrupting fluid barriers. The saccule is at particular risk due to its proximity to the surgical area and may explain immediate and long-term post-operative vertigo. Round window insertion may be less traumatic to the inner ear, however it may affect the vestibular receptors.

Three vascular routes to the inner ear are known: (a) through the internal acoustic meatus with the vestibulocochlear nerve; (b) from the endolymphatic duct aperture; and (c) along the canal of Cotugno (CC) inserted into the vestibular part of the ear from the superior or brain side. The third is believed to contain only veins. Examinations of 33 human embryos and fetuses at 6-40 weeks demonstrated that (a) the CC appeared as a recess of epidural mesenchymal tissues at the superior aspect of the otic capsule cartilage in embryos and it was inserted deeply to issue multiple peripheral divisions inferolaterally and posteriorly at midterm; (b) the CC consistently passed through a ring of the superior or anterior semicircular canal and contained both, the arteries from the vestibulocochlear nerve origin at the midbrain and the vein draining into the sigmoid sinus or petrosal sinuses; and (c) the CC appeared not to contribute to ossification of the otic capsule cartilage but, after endochondral ossification of the internal ear, woven bone development occurred along a smooth interface of the CC with the ossified ear. In contrast, another interface between the developing bone and the residual cartilage of the otic capsule was rough and wavy with many short bony columns, called osseous globules. In addition, the endolymphatic duct accompanied veins but no arteries. Our results show that the CC is a major vascular route to the vestibular part of the otic capsule cartilage, but its role appears to be limited after ossification.

Application of surgical endoscope, used alone or in combination with the surgical microscope, for the operative management of ear and temporal bone conditions may allow improved access and clearance of disease. Preservation of normal structures may also be improved.As the use of this tool is increasing, the need for better understanding of the anatomy of the ear is becoming evident. This is particularly so for endoscopic surgery aiming at removal of lesions involving the infra-cochlear corridor and/or petrous apex.Human temporal bone-derived labyrinth casts (molds), originally made for endolymphatic duct and sac analysis which genuinely represent the membranous labyrinth and its adjacent soft tissues, were morphometrically analyzed in terms of the anatomic relations between structures in and around the infra-cochlear corridor. The distance between the petrous carotid artery (PCA) and the basal turn of the cochlea, the distance between PCA and infra-cochlear vein (ICV)/cochlear aqueduct (CA), and the distance between the lower surface of basal cochlear turn and the point where the carotid artery and jugular vein (JV) meet close to the jugular foramen, were measured to be around 1.3 mm, 6 mm and 8 mm respectively, thus constituting an approximate 6 × 8 mm2 infra-cochlear corridor. This analysis and further study with larger samples might be helpful for operation via this corridor led to the petrous apex where cholesterol granuloma, cholesteatoma and other lesions are not uncommon. Keywords: Infra-cochlear corridor, Petrous apex, Anatomical study, Ear endoscopy, Surgery

PURPOSE Large endolymphatic duct and sac (LEDS) is one of the most common imaging abnormalities in congenital sensorineural hearing loss and is frequently seen with coexistent cochlear anomalies, especially incomplete partition type II. However, MRI findings of accompanying cochlear and especially modiolar dysplasias may be subtle. The purpose of this study is to evaluate the imaging findings of LEDS with high-resolution imaging at 3 T and correlate with the audiological data. METHODS 3 T temporal bone MRIs of 54 ears in 30 LEDS patients were retrospectively evaluated. The cochlear dysmorphism and modiolar deficiency were assessed qualitatively and quantitatively. The severity of LEDS anomaly, the signal changes within the LEDS and cochlea were also noted. The imaging findings were correlated to the audiological data. RESULTS The cochlea was abnormal in 77.8% of the ears with an isolated modiolar deficiency in 11.1%. Cochlea and modiolus were completely normal in 11.1% of the ears. In 63% of the ears X-distance was increased. T2 hypointensity within LEDS and cochlea were detected in 42.6%, and 7.4% of the ears, respectively. The median diameters of LEDS were higher in ears with severe to profound HL than ears with normal to moderate HL (p

Objective The purpose of the study was to investigate the difference in the responses of endolymphatic hydrostatic pressure to isoproterenol, β-adrenergic receptor agonist, between pars superior and pars inferior. Methods The hydrostatic pressure of endolymph and perilymph and endolymphatic potential in the ampulla and the cochlea during the intravenous administration of isoproterenol were recorded using a servo-null system in guinea pigs. Results The hydrostatic pressure of endolymph and perilymph in the ampulla and cochlea was similar in magnitude. Isoproterenol significantly increased hydrostatic pressure of ampullar and cochlear endolymph and perilymph with no change in the ampullar endolymphatic potential and endocochlear potential, respectively. The isoproterenol-induced maximum change of endolymphatic hydrostatic pressure in ampulla was significantly (p

Hizli, Omer/0000-0001-6822-2679; (Bingol) Hizli, Pelin/0000-0001-8919-3125 WOS: 000383312600004 PubMed: 26860231 Objective: To observe any changes in stria vascularis and cochlear hair cells in patients with syphilis. Materials and methods: We examined 13 human temporal bone samples from 8 patients with syphilis (our syphilis group), as well as 12 histopathologically normal samples from 9 age-matched patients without syphilis (our control group). We compared, between the two groups, the mean area of the stria vascularis (measured with conventional light microscopy connected to a personal computer) and the mean percentage of cochlear hair cell loss (obtained from cytocochleograms). Results: In our syphilis group, only 1 (7.7%) of the 13 samples had precipitate in the endolymphatic or perilymphatic spaces; 8 (61.5%) of the samples revealed the presence of endolymphatic hydrops (4 cochlear, 4 saccular). The mean area of the stria vascularis did not significantly differ, in any turn of the cochlea, between the 2 groups (P > 0.1). However, we did find significant differences between the 2 groups in the mean percentage of outer hair cells in the apical turn (P < 0.026) and in the mean percentage of inner hair cells in the basal (P = 0.001), middle (P = 0.004), and apical (P = 0.018) turns. In 7 samples in our syphilis group, we observed either complete loss of the organ of Corti or a flattened organ of Cord without any cells in addition to the absence of both outer and inner hair cells. Conclusion: In this study, syphilis led either to complete loss of the organ of Corti or to significant loss of cochlear hair cells, in addition to cochleosaccular hydrops. But the area of the stria vascularis did not change. (C) 2016 Elsevier Ireland Ltd. All rights reserved. NIH (NIDCD)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Deafness & Other Communication Disorders (NIDCD) [U24 DC011968-01]; International Hearing Foundation; Starkey Foundation; 5M Lions International; Scientific and Technological Research Council of Turkey (TUBITAK) ScholarshipTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) This project was funded by NIH (NIDCD), grant number U24 DC011968-01; the International Hearing Foundation; the Starkey Foundation; and the 5M Lions International. Omer Hizh and Serdar Kaya received the Scientific and Technological Research Council of Turkey (TUBITAK) Scholarship.

Meniere’s disease remains enigmatic, and has no treatment with sufficient evidence. The characteristic histopathological finding is endolymphatic hydrops, suggesting either an overproduction or decreased reabsorption of endolymph in the human inner ear. This study presents the first analysis of the vascular plexus around the human endolymphatic duct using micro computed tomography and coherent synchrotron radiation with phase contrast imaging. Using a software program, data were processed by volume-rendering with scalar opacity mapping to create transparent three-dimensional reconstructions. A rich vascular plexus was discovered around the endolymphatic duct that drained into collecting channels, linked to the vestibular venous outflow system. This network is believed to make up the principal route for endolymph outflow, and its associated malfunction may result in endolymphatic hydrops and Meniere’s disease. De tre sista författarna delar sistaförfattarskapet

Background: The endolymphatic sac (ES) is a cystic structure situated on the posterior fossa dura and is connected to the luminal space of the vestibular organ through the endolymphatic duct, which branches into the utricular and saccular ducts. Unlike the cochlea and vestibule, the ES does not contain sensory epithelium in its luminal space, and a single layer of epithelial cells line the luminal surface area. The ES in the inner ear is thought to play a role in the regulation of inner ear homeostasis, fluid volume, and immune reaction. If these functions of the ES are disrupted, dysfunction of the inner ear may develop. The most well-known pathology arising from dysfunction of the ES is endolymphatic hydrops, characterized by an enlarged endolymphatic space due to the accumulation of excessive endolymphatic fluid. Although, molecular identities and functional evidence for the roles were identified in animal studies, basic studies of the human ES are relatively uncommon compared with those using animal tissues, because of limited opportunity to harvest the human ES. Methods: In this study, molecular and functional evidence for the role of the human ES in the development of endolymphatic hydrops are reviewed. Results and Conclusions: Although evidence is insufficient, studies using the human ES have mostly produced findings similar to those of animal studies. This review may provide a basis for planning further studies to investigate the pathophysiology of disorders with the finding of endolymphatic hydrops.

The lower stations of the auditory system display a complex anatomy. The inner ear labyrinth is composed of several interconnecting membranous structures encased in cavities of the temporal bone, and the cerebellopontine angle contains fragile structures such as meningeal folds, the choroid plexus (CP), and highly variable vascular formations. For this reason, most histological studies of the auditory system have either focused on the inner ear or the CNS by physically detaching the temporal bone from the brainstem. However, several studies of neuroimmune interactions have pinpointed the importance of structures such as meninges and CP; in the auditory system, an immune function has also been suggested for inner ear structures such as the endolymphatic duct (ED) and sac. All these structures are thin, fragile, and have complex 3D shapes. In order to study the immune cell populations located on these structures and their relevance to the inner ear and auditory brainstem in health and disease, we obtained a clarified-decalcified preparation of the rat hindbrain still attached to the intact temporal bone. This preparation may be immunolabeled using a clearing protocol (based on iDISCO+) to show location and functional state of immune cells. The observed macrophage distribution suggests the presence of CP-mediated communication pathways between the inner ear and the cochlear nuclei., Frontiers in Neuroanatomy, 13, ISSN:1662-5129

Melanin pigmentation is present in the human inner ear. In this study, we quantify the melanin pigmentation in the vestibular system and examine racial differences of vestibular melanin pigmentation using human cadaveric temporal bone specimens.Basic research.Laboratory.Light microscopy was used to examine specimens from 40 left temporal bones from the Johns Hopkins Human Temporal Bone Collection. Color images of (1) ampulla of the horizontal canal, (2) utricular wall, (3) endolymphatic duct, and (4) posterior ampullary nerve as it enters the posterior canal were acquired with a digital camera attached to the microscope and image acquisition software. Acquired images of each anatomic area of interest were processed offline through ImageJ. Melanin content was then compared according to ethnicity, age, sex, and location.Fifteen African American and 25 Caucasian specimens were analyzed. Mean age was 68.8 years. African American specimens had a significantly greater amount of pigment at all 4 sampled locations as compared with Caucasian specimens (P.01). Between sexes, there was a statistically significant difference (P.05) at the posterior ampullary nerve, with males having more than females. Melanin content was not associated with age.There is greater melanin pigmentation within the vestibular system of African Americans than in Caucasians, similar to what has been described in the cochlea. Racial differences in vestibular physiologic function have been observed in the literature and may be explained by differences in melanin pigmentation.

Purpose During vestibular schwannoma surgery there is a risk of endolymphatic duct and sac injury, which may cause a loss or a deterioration of hearing. The goal of the study was to evaluate the empirical utility of presurgical planning using CT with the bone window for the hearing preservation surgery. Methods The study was performed on 14 human temporal bones. CT scans with the bone window were obtained in the standard position. Safe drilling line was evaluated and after that drilling distances were analysed: the lateral drilling distance, total length of internal acoustic meatus, drilled length of internal acoustic meatus. After this, a surgical exposure was performed, using size of a drill tip as measuring scale. The dura was excised and endolymphatic duct was injected with a latex. Revision of the internal acoustic meatus was performed with the use of a microscope. Results Mean results of safe drilling coefficients were: lateral drilling distance: 10 ± 2 mm, total length of internal acoustic meatus: 9 ± 2 mm, drilled length of internal acoustic meatus: 7 ± 2 mm. In all cases, no endolymphatic duct injury was observed. Conclusions Preoperative radiological planning using the safe drilling coefficients is of value for the hearing preservation surgery in vestibular schwannoma. The size of the drilling tip may be used as an intraoperative measuring scale during this procedure. However, CT with a bone window is a necessary tool for the purposes of this procedure.

Preparation of the temporal bone for light microscopy is an important step in histological studies of the inner ear. Due to the complexity of structures of the inner ear, it is difficult to measure or compare structures of interest without a commonly accepted standardized measure of temporal bone sections. Therefore, standardization of temporal bone sections is very important for histological assessment of sensory hair cells and peripheral ganglion neurons in the cochlear and vestibular systems. The standardized temporal bone sectioning is oriented to a plane parallel to the outer and internal auditory canals. Sections are collected from the epitympanum to the hypotympanum to reveal layers in the order of the crista ampullaris of the superior and lateral semicircular canals, macula utriculi and macula sacculi, superior vestibular ganglion neurons, macula of saccule and inferior vestibular ganglion neurons, cochlear modiolus, endolymphatic duct and endolymphatic sac, and finally the crista ampullaris of the posterior semicircular canal. Moreover, technical details of preparing for temporal bone sectioning including fixation, decalcification, whole temporal bone staining, embedding penetration, and embedding orientation are also discussed.

Introduction Endolymphatic sac tumours are benign, slowly growing tumours that invade the temporal bone, and present clinically in the form of unilateral hearing loss. They can be sporadic or occur in the context of Von Hippel-Lindau disease (VHL). Case summary The authors report a case of endolymphatic sac tumour arising in the utricle presenting histological and immunohistochemical features corresponding to endolymphatic sac tumour in a patient without VHL. Discussion Endolymphatic sac tumours invade the posterior part of the petrous temporal bone. According to two studies concerning patients with Von Hippel-Lindau disease, endolymphatic sac tumours arise from the endolymphatic duct. This case of intralabyrinthine sporadic endolymphatic sac tumour supports this hypothesis for sporadic forms, indicating the need for labyrinthectomy associated with tumour resection to avoid recurrence.

Meniere's disease is an inner ear disorder characterized by vertigo attacks, fluctuating and progressive hearing loss, tinnitus, and aural fullness in the affected ear. The pathophysiology of Meniere's disease remains elusive. Theories so far are anatomical variation in the size or position of the endolymphatic sac and duct, viral inflammation or autoimmune involvement of the sac, or a genetically determined abnormality of endolymph control. Animal studies on blocking the ductus reuniens and endolymphatic duct have produced hydrops in the cochlea, saccule, and utricle. Cone beam computed tomography images show a similar pattern with apparent obstruction of the ductus reuniens, saccular duct, and endolymphatic sinus. New studies documenting the age of onset of Meniere's disease show a pattern similar to benign paroxysmal positional vertigo, raising the possibility that the fundamental cause of Meniere's disease might be detached saccular otoconia.

Control over ionic composition and volume of the inner ear luminal fluid endolymph is essential for normal hearing and balance. Mice deficient in either the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2 (Efnb2) exhibit background strain-specific vestibular-behavioral dysfunction and signs of abnormal endolymph homeostasis. Using various loss-of-function mouse models, we found that Efnb2 is required for growth and morphogenesis of the embryonic endolymphatic epithelium, a precursor of the endolymphatic sac (ES) and duct (ED), which mediate endolymph homeostasis. Conditional inactivation of Efnb2 in early-stage embryonic ear tissues disrupted cell proliferation, cell survival, and epithelial folding at the origin of the endolymphatic epithelium. This correlated with apparent absence of an ED, mis-localization of ES ion transport cells relative to inner ear sensory organs, dysplasia of the endolymph fluid space, and abnormally formed otoconia (extracellular calcite-protein composites) at later stages of embryonic development. A comparison of Efnb2 and Notch signaling-deficient mutant phenotypes indicated that these two signaling systems have distinct and non-overlapping roles in ES/ED development. Homozygous deletion of the Efnb2 C-terminus caused abnormalities similar to those found in the conditional Efnb2 null homozygote. Analyses of fetal Efnb2 C-terminus deletion heterozygotes found mis-localized ES ion transport cells only in the genetic background exhibiting vestibular dysfunction. We propose that developmental dysplasias described here are a gene dose-sensitive cause of the vestibular dysfunction observed in EphB–Efnb2 signaling-deficient mice.

Primary adenomatous and adenocarcinomatous lesions of the temporal bone are rare tumors. Primary low-grade papillary adenocarcinomas of the endolymphatic sac origin were first reported by Heffner. These lesions, which are referred to as "Heffner tumors," are slow-growing, bone-destructive infiltrating tumors. Owing to the local bone destruction (usually centered at posterior petromastoid plate), the general consensus favors the endolymphatic sac as being the origin of these tumors. However, controversies regarding the cellular origins of adenomatous tumors of the temporal bone have been reported. Mafee and Shah reported a unique case in which histology was identical to papillary adenocarcinoma of endolymphatic sac in which the sac and duct showed normal findings on magnetic resonance images, which were confirmed on surgery. Computed tomography and magnetic resonance imaging are excellent imaging methods for evaluation of normal and anomaly of the vestibular aqueduct and endolymphatic duct and sac and for the diagnosis of these endolymphatic tumors. This article reviews computed tomography and magnetic resonance imaging characteristics of adenocarcinomatous tumors of temporal bone. This report also concerns a unique case of a papillary adenocarcinoma of presumed endolymphatic sac in a 12-year-old child, in which tumor replaced almost the entire petromastoid resulting in a markedly egg-shell appearance of the bone. To the best of our knowledge, this is the youngest child with papillary endolymphatic sac tumor reported.

Objectives/Hypothesis To measure the volume of the endolymph drainage system in temporal bone specimens with Meniere disease, as compared with specimens with endolymphatic hydrops without vestibular symptoms and with nondiseased specimens Study Design Comparative human temporal bone analysis. Methods We generated three-dimensional models of the vestibular aqueduct, endolymphatic sinus and duct, and intratemporal portion of the endolymphatic sac and calculated the volume of those structures. We also measured the internal and external aperture of the vestibular aqueduct, as well as the opening (if present) of the utriculoendolymphatic (Bast's) valve and compared the measurements in our three study groups. Results The volume of the vestibular aqueduct and of the endolymphatic sinus, duct, and intratemporal endolymphatic sac was significantly lower in the Meniere disease group than in the endolymphatic hydrops group (P

Background The pathogenesis of Meniere disease (MD) has not been fully understood. According to the widely accepted theory, imbalances due to overproduction and/or impaired absorption of endolymph may cause endolymphatic hydrops, which is the hallmark pathological finding in MD. Some developmental temporal bone abnormalities may impair endolymph circulation and absorption, and these abnormalities could be a part of MD pathophysiology. However, structural features of the temporal bone cannot explain MD pathophysiology definitively. The authors aimed to determine the length and width of the endolymphatic duct (ED) along with jugular bulb (JB) abnormalities in MD patients and normal controls using high-resolution computed tomography, and to discuss the results supporting and opposing endolymphatic hydrops based on the data obtained. Methods Thirty-six ears of 18 patients with unilateral MD and 34 ears of 17 normal subjects were enrolled. Jugular bulb abnormalities and ED dimensions were evaluated in 3 groups: affected and unaffected ears of MD patients, and healthy controls. The ED dimensions and JB abnormalities were evaluated with high-resolution computed tomography. Results The ED was found to be significantly shorter and narrower in the affected ears of the MD patients than in the healthy control group. In addition, more JB abnormalities were detected in the affected ears of the MD patients than in the healthy control group. However, there was no difference between the affected and unaffected ears of the MD patients. Conclusion Structural ED abnormalities and JB abnormalities may be predisposing factors for the development of Meniere disease, but cannot fully explain MD pathophysiology.

There are a variety of techniques available to investigate endolymph dynamics, primarily seeking to understand the cause of endolymphatic hydrops. Here we have taken the novel approach of injecting, via a glass micropipette, fluorescein isothiocyanate-dextran (FITC-dex) and artificial endolymph into scala media of anaesthetized guinea pigs, with subsequent imaging of the inner ear using Light Sheet Fluorescence Microscopy (LSFM) as a means to obtain highly resolved 3D visualization of fluid movements. Our results demonstrate endolymph movement into the utricle, semicircular canals and endolymphatic duct and sac when more than 2.5 μl of fluid had been injected into scala media, with no apparent movement of fluid into the perilymphatic compartments. There was no movement of endolymph into these compartments when less than 2.5 μl was injected. The remarkable uptake of the FITC-dex into the endolymphatic duct, including an absorption into the periductal channels surrounding the endolymphatic duct, highlights the functional role this structure plays in endolymph volume regulation.

Conclusion: Blockage of the endolymphatic duct is a significant finding in Meniere's disease. The position of the utriculo-endolymphatic valve (UEV) and blockage of the ductus reuniens in the temporal bones were not found to be directly indicative of Meniere's disease. Objective: Comparison of blockage of the longitudinal flow of endolymph between ears affected by Meniere's disease and normal ears. Methods: We examined 21 temporal bones from 13 subjects who had Meniere's disease and 21 normal temporal bones from 12 controls. Results: The endolymphatic duct was blocked in five (23%) ears affected by Meniere's disease (p = 0.016). The utricular duct was blocked in 16 (76%) ears affected by Meniere's disease and 11 (52%) normal ears (p = 0.112). The saccular duct was blocked in 6 (28%) of ears affected by Meniere's disease and 16 (76%) normal ears (p = 0.001). The ductus reuniens was blocked in 10 (47%) ears affected by Meniere's disease and 10 (47%) normal ears (p = 1.000).

Haploinsufficiency of Gata3 causes hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome in mice and humans. Gata3 null mutation leads to early lethality around embryonic day (E)11.5, but catecholamine precursor administration can rescue Gata3 null mutants to E16.5. At E11.5, GATA3 deficiency results in the development of an empty otocyst with an endolymphatic duct. However, using rescued mice we found that some morphogenesis and neurosensory development is possible in the ear without Gata3. Extending previous studies, we find that at E16.5, Gata3 mutant inner ears can undergo partial morphogenesis and develop an endolymphatic duct, a utricular and saccular recess, and a shortened cochlear duct. In addition to the obvious morphogenic aberrations, these studies demonstrate that a subset of neurons develop and connect a fragmented sensory patch of MYO7A-positive hair cells to the vestibular nuclei of the brainstem. In situ hybridization studies reveal altered expression of several transcription factors relevant to ear development and we hypothesize that this may relate to the observed dysmorphia and restricted neurosensory development. While a cochlear duct can form, there is no concurrent cochlear neurosensory development, observations consistent with specific hearing defects encountered by HDR patients and mice with Gata3-associated expression alterations. Gata3 null mutant phenocopies the otic maldevelopment (cochlear duct formation in the absence of neurosensory development) seen in Foxg1cre mediated conditional deletion of microRNA processing enzyme, Dicer1. Finally, while GATA3 is expressed in the developing vestibulo-cochlear efferent (VCE) neurons, and its absence in the null mutants disrupts VCE projections to the ear, loss of GATA3 does not affect VCE progenitor cell migration.

A developmental histologic study of the otic capsule indicates that it grows a system of lamellar bone with abundant interconnecting intraosseous channels. These include the 'cartilage canals' in the cartilage model, the chondro-osseous and Haversian-like (Volkmann's) canals in the ossified otic capsule, the fissula ante fenestram, which seems to function as a lifelong manufacturer of the latter two channels, and the inner layer (vestibular arch) of the vestibular aqueduct, which is a complex series of Volkmann's canals and microcanals. Chemical changes, possibly produced by breakdown of cells within the channels, may provide a homeostatic environment for the functions of hearing and balance that take place in the endolymphatic fluid.We studied the development of the otic capsule to clarify the cellular appearances that we had previously described in the normal vestibular arch and the changes in that structure in Ménière's disease.Step sections from 84 temporal bones, including those from fetuses, children and adults from a variety of ages were examined histologically.Cartilage canals, bringing blood vessels and mesenchymal cells from perichondrium to the depths of the cartilage model to mediate ossification, are found early in fetal life and disappear when ossification is complete at about 24 weeks. The otic capsule is formed of chondro-osseous canals, which are composed of trabeculae of mineralized cartilage lacunae containing mesenchymal cells that undergo ossification (globuli ossei); also Volkmann's canals (like Haversian canals in long bones but multidirectional), which are produced from osteoblasts. The lumina of the latter frequently link up with chondro-osseous canals. Lamellar bone forms the background of the otic capsule. The fissula ante fenestram is present from early in the cartilage model and then throughout life. It appears to mediate bone production and the new formation of chondro-osseous channels and Volkmann's canals. The internal layer of the vestibular aqueduct (vestibular arch) is seen in the cartilage model of the otic capsule (present in early fetal life) as a vascular layer of perichondrally derived connective tissue (not cartilage) surrounding the endolymphatic duct. When endochondral ossification starts, the bone from the adjoining cochlear and vestibular sides embrace this connective tissue layer to form the outer bony layer of the vestibular aqueduct. Osteoblasts then fill the inner layer with lamellar bone and macro- and mini-Volkmann's canals. At 1 year osteoblasts in the walls of macro-Volkmann's canals, proliferating thereafter throughout life, produce large numbers of microcanals. It is possible that slow breakdown of these osteoblasts and of similar cells in the canals of the otic capsule proper may contribute to the homeostasis of the endolymphatic duct and that of the rest of the membranous labyrinth, respectively.

The first description of the presence of a utriculo-endolymphatic valve in human fetuses was given by Bast in 1928. Since then this valve-like structure is called Bast's valve. Its exact function has not yet been established. The general opinion is that it has a protective function by having the possibility to separate the superior endolymphatic compartments of the labyrinth from the inferior compartment. Phylogenetically seen birds are the first vertebrates with a cochlear duct and a distinct inferior and superior part of the labyrinth. A structure in the pigeon inner ear, resembling Bast's valve in mammals, is described.

Conclusions. That the endolymphatic sac (ES) reacts to changes in inner ear blood flow may be important for homeostasis of the inner ear fluid volume and pressure. Objectives. To elucidate the effect of changes in inner ear blood flow on the ES and to learn more about the volume and pressure regulatory function of the ES. Materials and methods. Epinephrine or sodium nitroprusside (SNP) was injected into the middle ear cavity of adult CBA/J mice. The ES were analyzed morphologically by light microscopy. Results. Epinephrine reduced the luminal size of the ES leading to an accumulation of intraluminal homogeneous substance. Injection of SNP increased the size of the ES lumen, accompanied by a collapse of the lateral intercellular space (LIS) and dense perisaccular tissue. These changes were almost reversed 4 h after injection.

An enlarged endolymphatic duct and sac (EDS) that makes contact with the cerebrospinal fluid–dural interface plays an important role in the pathway of bone conduction and enhances bone conduction at lower frequencies. Objectives. We investigated whether the bone conduction threshold was improved when the EDS was enlarged. Subjects and methods. Twenty-three patients (46 ears) with large vestibular aqueducts underwent standard pure tone audiometry (PTA) and magnetic resonance imaging (MRI) to investigate the relation between the diameter of the endolymphatic duct (ED) and the air or bone conduction threshold. We also investigated the relation between the volume of the EDS and the air or bone conduction threshold. Results. All ears had a mixed type hearing loss. The air–bone gaps were significantly larger at 250 and 500 Hz than at higher frequencies. The bone conduction thresholds were significantly lower at 250 Hz and 1000 Hz when the diameter of the ED was large, whereas there was no relation between the diameter of the ED and the air conduction threshold. In addition, there was no correlation between the volume of the EDS and air or bone conduction thresholds.

The inner ear, which contains sensory organs specialized for hearing and balance, develops from an ectodermal placode that invaginates lateral to hindbrain rhombomeres (r) 5-6 to form the otic vesicle. Under the influence of signals from intra- and extraotic sources, the vesicle is molecularly patterned and undergoes morphogenesis and cell-type differentiation to acquire its distinct functional compartments. We show in mouse that Fgf3 , which is expressed in the hindbrain from otic induction through endolymphatic duct outgrowth, and in the prospective neurosensory domain of the otic epithelium as morphogenesis initiates, is required for both auditory and vestibular function. We provide new morphologic data on otic dysmorphogenesis in Fgf3 mutants, which show a range of malformations similar to those of Mafb ( Kreisler ), Hoxa1 and Gbx2 mutants, the most common phenotype being failure of endolymphatic duct and common crus formation, accompanied by epithelial dilatation and reduced cochlear coiling. The malformations have close parallels with those seen in hearing-impaired patients. The morphologic data, together with an analysis of changes in the molecular patterning of Fgf3 mutant otic vesicles, and comparisons with other mutations affecting otic morphogenesis, allow placement of Fgf3 between hindbrain-expressed Hoxa1 and Mafb , and otic vesicle-expressed Gbx2 , in the genetic cascade initiated by WNT signaling that leads to dorsal otic patterning and endolymphatic duct formation. Finally, we show that Fgf3 prevents ventral expansion of r5-6 neurectodermal Wnt3a , serving to focus inductive WNT signals on the dorsal otic vesicle and highlighting a new example of cross-talk between the two signaling systems.

During vertebrate inner ear development, compartmentalization of the auditory and vestibular apparatuses along two axes depends on the patterning of transcription factors expressed in a region-specific manner. Although most of the patterning is regulated by extrinsic signals, it is not known how Nkx5.1 and Msx1 are patterned. We focus on Dan, the founding member of the Cerberus/Dan gene family that encodes BMP antagonists, and describe its function in morphogenesis and patterning. First, we confirmed that Dan is expressed in the dorso-medial region of the otic vesicle that corresponds to the presumptive endolymphatic duct and sac (ed/es). Second, we used siRNA knockdown to demonstrate that depletion of Dan induced both a severe reduction in the size of the ed/es and moderate deformities of the semicircular canals and cochlear duct. Depletion of Dan also caused suppression of Nkx5.1 in the dorso-lateral region, suppression of Msx1 in the dorso-medial region, and ectopic induction of Nkx5.1 and Msx1 in the ventro-medial region. Most of these phenotypes also appeared following misexpression of the constitutively active form of BMP receptor type Ib. Thus, Dan is required for the normal morphogenesis of the inner ear and, by inhibiting BMP signaling, for the patterning of the transcription factors Nkx5.1 and Msx1.

Objective: To describe temporal bone findings on computed tomography (CT) imaging in GJB2-related hearing loss (HL). We asked whether evaluation of the temporal bone is required in individuals with biallelic GJB2 mutations. Study Design: Randomized, blinded, controlled, prospective measurement. Methods: Blood from 264 pediatric cochlear implant users was analyzed for mutations in the GJB2 gene. Thirtysix aspects of the temporal bone on CT imaging were evaluated in 53 individuals (106 ears) with biallelic disease causing GJB2 mutations. A subset of patients was age matched and compared with normally hearing individuals. Subjects with biallelic GJB2 mutations were tested for mutations in the SLC26A4 gene to rule out Pendred syndrome as a confounding cause of large vestibular aqueduct syndrome. Results: Approximately 53% of ears of subjects (72% of subjects) with biallelic GJB2 mutations had at least one temporal bone anomaly. The most common findings were 1) dilated endolymphatic fossa (28%); 2) hypoplastic modiolus (25%); 3) large vestibular aqueduct (8%); 4) hypoplastic horizontal semicircular canal (8%); 5) hypoplastic cochlea (4%). Compared with normally hearing individuals, the GJB2 group had hypoplasia of the cochlear nerve canal, lateral semicircular canal vestibule, internal auditory canal (t tests, P < .001), and were 11 times more likely to have a hypoplastic modiolus. Dilated endolymphatic fossae were 1.4 times more common in the GJB2 group, and large vestibular aqueducts were 3 times more common in the GJB2 group, as compared with normally hearing controls. Conclusions: Temporal bone anomalies are common in GJB2-related HL, and imaging of the temporal bone should be included in routine evaluation of these individuals. Key Words: Temporal bone, tomography, CT, GJB2, connexins, measure, Pendred, SLC26A4. Laryngoscope, 116:2178–2186, 2006

A vestibular aqueduct midpoint width greater than 1.50 mm is currently considered to be pathognomonic for a large vestibular aqueduct syndrome. To analyse the diameter of the vestibular aqueduct in children as a function of age and consequently to determine if a fixed measure could serve as a pertinent diagnostic criterion. This was a retrospective study of 200 high-resolution CT scans of the ear in 100 patients aged 0–16 years and from various paediatric medical departments. On each CT scan, the lateral semicircular canal diameter, the vestibular aqueduct midpoint width between the external aperture and common crus, and the vestibular aqueduct external aperture diameter were measured. Spearman’s rank test and the Mann-Whitney correlation test were used for an integrated statistical analysis. There was no statistically significant variability in vestibular aqueduct diameter as a function of age or sex of patients. A CT scan threshold value, fixed and independent of age and sex, is thus legitimate for the diagnosis of vestibular aqueduct dilatation.

We report a case of endolymphatic sac tumor (ELST). A 48-year-old female had recurrent and slowly progressive hearing loss, accompanied with dizziness like Meniere's disease. A tumor was located around the semicircular canals, and was detected on CT and MRI. The patient underwent total removal of the tumor using a transmastoid approach. Histopathological examinations agreed with features of an ELST. The tumor was highly suspected to have originated from the rugose portion of the endolymphatic sac or the endolymphatic duct, based on surgical and imaging studies. Structure of the membranous labyrinth was preserved regardless of the existence of the tumor around semicircular canals with bone destruction. ELSTs seem to have an osteolytic or osteophilic nature, by examining patterns of tumor infiltration.

SummaryIn experimental endolymphatic hydrops distortion-products otoacoustic emission (dpoae) amplitudes decrease and there is elevation on electrocochleographic thresholds. Some authors found type ii nitric oxide synthase (nos ii) expression in hydropic cochleas and they suggest nitric oxide (no) may be involved in endolymphatic hydrops pathogenesis. The aim of this study was to evaluate the action of a nos ii inhibitor on dpoae and electrocochleography in experimental endolymphatic hydrops. Material and methods: endolymphatic hydrops was induced in 16 guinea pigs by obliterating the endolymphatic duct and sac in the right ear. They were divided in two groups: eigth guinea pigs under the action of aminoguanidine, a nos ii inhibitor and eigth control guinea pigs. We compared dpoae amplitudes at geometric means of frequencies 1062, 2187, 4375 and 7000 hz, compound action potential threshold at 1000, 2000, 4000 and 6000 hz and summating potential to action potential (sp/ap) ratio between the groups during the postoperative observation period of 16 weeks. Results: there were no significant changes in the dpoae amplitudes and in the sp/ap ratio. The group that received aminoguanidine had a lower degree of threshold increase at 2000 (p

Optical coherence tomography (OCT) has advanced significantly over the past two decades and is currently used extensively to monitor the internal structures of organs, particularly in ophthalmology and dermatology. We used ethylenediamine tetra-acetic acid (EDTA) to decalcify the bony walls of the cochlea and investigated the inner structures by deep penetration of light into the cochlear tissue using OCT on a guinea pig model of endolymphatic hydrops (EH), induced by surgical obliteration of the endolymphatic duct. The structural and functional changes associated with EH were identified using OCT and auditory brainstem response tests, respectively. We also evaluated structural alterations in the cochlea using three-dimensional reconstruction of the OCT images, which clearly showed physical changes in the cochlear structures. Furthermore, we found significant anatomical variations in the EH model and conducted graphical analysis by strial atrophy for comparison. The physical changes included damage to and flattening of the organ of Corti—evidence of Reissner's membrane distention—and thinning of the lateral wall. These results indicate that observation of EDTA-decalcified cochlea using OCT is significant in examination of gradual changes in the cochlear structures that are otherwise not depicted by hematoxylin and eosin staining.

Gbx2 is a homeobox-containing transcription factor that is related to unplugged in Drosophila. In mice, Gbx2 and Otx2 negatively regulate each other to establish the mid-hindbrain boundary in the neural tube. Here, we show that Gbx2 is required for the development of the mouse inner ear. Absence of the endolymphatic duct and swelling of the membranous labyrinth are common features in Gbx2-/- inner ears. More severe mutant phenotypes include absence of the anterior and posterior semicircular canals, and a malformed saccule and cochlear duct. However, formation of the lateral semicircular canal and its ampulla is usually unaffected. These inner ear phenotypes are remarkably similar to those reported in kreisler mice, which have inner ear defects attributed to defects in the hindbrain. Based on gene expression analyses, we propose that activation of Gbx2 expression within the inner ear is an important pathway whereby signals from the hindbrain regulate inner ear development. In addition, our results suggest that Gbx2 normally promotes dorsal fates such as the endolymphatic duct and semicircular canals by positively regulating genes such as Wnt2b and Dlx5. However, Gbx2 promotes ventral fates such as the saccule and cochlear duct, possibly by restricting Otx2 expression.

The extensive remains of large sauropods, excavated in the Upper Jurassic layers of the Tendaguru region of Tanzania, East Africa by Janensch [15], include an intact fossil cast of a vestibular labyrinth and an endocast of the large Brachiosaurus brancai. The approximately 150 million year old labyrinth cast demonstrates clearly a form and organisation congruent in detail to those of extant vertebrate species. Besides the near-orthogonal arrangement of semicircular canals (SCCs), the superior and inferior branches of the vestibulo-acoustic nerve, the endolymphatic duct, the oval and round windows, and the cochlea can be identified. The orientation of the labyrinth in the temporal bone is also equivalent to that of many extant vertebrates. Furthermore, the existence of the twelve cranial nerves can be identified from the endocast. The present study was initiated after the photogrammetric measurement of the skeleton volume of B. brancai [13] yielded a realistic estimate of body mass (74.42 metric tons). Dimensional analysis shows that body mass and average SCC dimensions of B. brancai generally fit with the allometric relationship found in previous studies of extant species. However, the anterior SCC is significantly larger than the allometric relationship would predict. This would indicate greater sensitivity, supporting the idea that the behavioural repertoire must have included much slower pitch movements of the head. These slower movements would most likely have involved flexion of the neck, rather than head pitching about the atlas joint. Pursuing the relationship between body mass and SCC dimensions further, the SCC frequency response is estimated by scaling up from the SCC dimensions of the rhesus monkey; this yields a range between 0.008–26 Hz, approximately one octave lower than for humans.

The chick inner ear is a complex structure containing auditory and vestibular sensory organs innervated by neurons of the acoustic-vestibular ganglion. The molecular signals involved in the specification and initial innervation of the otic epithelium are poorly understood. Here, we present a detailed description of the Otx2, Gbx2, and Fgf8 gene expression patterns in the chick developing inner ear, comparing them with the Bmp4 expression, a putative sensory-organ marker. The Otx2 expression was detected in the ventro-lateral wall of the otic anlage and could play a role in the segregation of the saccule and utricle maculae. The relationship between Gbx2 and Fgf8 expression changed during inner ear development but was always related to the macula sacculi innervation and endolymphatic duct formation. Our results also suggest that the maculae of the saccule and lagena, and the medial portion of the macula utriculi could arise within a broad Fgf8-positive domain previously observed at the otocyst stage. The spatial and temporal relationships between these gene expression domains and the initial innervation of the epithelium by some subpopulations of otic axons suggest that expression domain boundaries could be involved in the specification and early innervation of presumptive sensory patches.

The human endolymphatic duct (ED) and sac of the inner ear have been suggested to control endolymph volume and pressure. However, the physiological mechanisms for these processes remain obscure. We investigated the organization of the periductal interstitial connective tissue cells and extracellular matrix (ECM) in four freshly fixed human EDs by transmission electron microscopy and by immunohistochemistry. The unique surgical material allowed a greatly improved structural and epitopic preservation of tissue. Periductal connective tissue cells formed frequent intercellular contacts and focally occurring electron-dense contacts to ECM structures, creating a complex tissue network. The connective tissue cells also formed contacts with the basal lamina of the ED epithelium and the bone matrix, connecting the ED with the surrounding bone of the vestibular aqueduct. The interstitial connective tissue cells were non-endothelial and non-smooth muscle fibroblastoid cells. We suggest that the ED tissue network forms a functional mechanical entity that takes part in the control of inner ear fluid pressure and endolymph resorption.

Mice that lack the winged helix/forkhead gene Foxi1 (also known as Fkh10) are deaf and display shaker/waltzer behavior, an indication of disturbed balance. While Foxi1 is expressed in the entire otic vesicle at E9.5, it becomes gradually restricted to the endolymphatic duct/sac epithelium and at E16.5 Foxi1 expression in the inner ear is confined to this epithelium. Histological sections, paintfill experiments and whole-mount hybridizations reveal no abnormality in inner ear development of Foxi1-/- mice before E13.5. Between E13.5 and E16.5 the membranous labyrinth of inner ears from null mutants starts to expand as can be seen in histological sections, paint-fill experiments and three-dimensional reconstruction. Postnatally, inner ears of Foxi1-/- mice are extremely expanded, and large irregular cavities, compressing the cerebellum and the otherwise normal middle ear, have replaced the delicate compartments of the wild-type inner ear. This phenotype resembles that of the human sensorineural deafness syndrome Pendred syndrome, caused by mutations in the PDS gene. In situ hybridization of Foxi1-/- endolymphatic duct/sac epithelium shows a complete lack of the transcript encoding the chloride/iodide transporter pendrin. Based on this, we would like to suggest that Foxi1 is an upstream regulator of pendrin and that the phenotype seen in Foxi1 null mice is, at least in part, due to defective pendrin-mediated chloride ion resorption in the endolymphatic duct/sac epithelium. We show that this regulation could be mediated by absence of a specific endolymphatic cell type — FORE (forkhead related) cells — expressing Foxi1, Pds, Coch and Jag1. Thus, mutations in FOXI1 could prove to cause a Pendred syndrome-like human deafness.

An in vivo tracer was used to determine if the reticular lamina and/or the cell membranes abutting the endolymphatic space are temporarily disrupted after intense noise exposure (4-kHz OBN, 108-dB SPL, 1.75 h). Using a double-barreled micropipette, the endolymphatic potential (EP) was recorded and artificial endolymph containing 10% carbon particles was injected into the endolymphatic space either 0 days or 28 days post-exposure. The cochleae were fixed 30–45 min post-injection, then dehydrated, embedded in plastic and dissected as flat preparations. Damage in the organ of Corti (OC) was quantified, the location of carbon was determined, and some OC segments were then sectioned radially. EP averaged 72±5 mV in five controls. These cochleae had carbon tracer in the endolymphatic space only. Four of five noise-exposed chinchillas examined 3–4 h post-exposure had a low EP (30±6 mV). The cochleae from these 0-day animals had several focal lesions in which nearly all outer hair cells had just degenerated. At these lesions, carbon was attached to cell membranes and debris between the reticular lamina and basilar membrane. By transmission electron microscopy, discontinuities were found in the apical membranes of sensory and supporting cells. Carbon particles were found in the cytoplasm of these cells. Four of five animals examined at 28 days had an average EP of 70±11 mV. The cochleae from these animals had multiple lesions in the basal turn, all of which were healed by phalangeal scars or squamous epithelial cells. In these cochleae, no carbon was found within the OC. Acute disruption of the reticular lamina and the apical membranes of sensory and supporting cells from noise appears to be a major mechanism to account for degeneration in the cochlea that spreads or continues for days to weeks post-exposure.

Our previous research had suggested that beta-tubulin might be an autoantigen for autoimmune inner ear disease. In this study, the expression of beta-tubulin in inner ears of normal and tubulin-immunized guinea pigs was examined by immunohistochemical staining. Strong immunoreactivity to beta-tubulin monoclonal antibody was found in stria vascularis, neurons of the spiral ganglion, cochlear nerve fibers and spiral ligament. Diffuse staining was found in the stria vascularis and the neurons of the spiral ganglion, while dense network staining was found in the spiral ligament, the nerve fibers and the vestibular end organs. The semicircular canals, endolymphatic duct and sac were also positively stained. In inner ears of guinea pigs challenged with beta-tubulin, staining intensity was diminished in the stria vascularis, the spiral ligament, and the neurons of the spiral ganglion. The results suggest that beta-tubulin is distributed to most structures of guinea pig inner ear. A challenge to the inner ear by tubulin could change the beta-tubulin distribution and cause degeneration in the spiral ganglion. The results support the hypothesis that beta-tubulin might be an autoantigen for autoimmune inner ear disease.

Meniere's disease is a rare disorder that affects the inner ear which might be more severe if not treated. This is due to fluctuating pressure of the fluid in the endolymphatic sac and dysfunction of cochlea which causing the stretching of vestibular membrane. However, the pattern of the flow recirculation in endolymphatic region is still not fully understood. Thus, this study aims to investigate the correlation between the increasing volume of endolymphatic fluid and flow characteristics such as velocity, pressure and wall shear stress. Three dimensional model of simplified endolymphatic region is modeled using computer aided design (CAD) software and simulated using computational fluid dynamic (CFD) software. There are three different models are investigated; normal (N) model, Meniere's disease model with less severity (M1) and Meniere's disease model with high severity (M2). From the observed, the pressure drop between inlet and outlet of inner ear becomes decreases as the outlet pressure along with endolymphatic volume increases. However, constant flow rate imposed at the inlet of endolymphatic showing the lowest velocity. Flow recirculation near to endolymphatic region is occurred as the volume in endolympathic increases. Overall, high velocity is monitored near to cochlear duct, ductus reuniens and endolymphatic duct. Hence, these areas show high distributions of wall shear stress (WSS) that indicating a high probability of endolymphatic wall membrane dilation. Thus, more severe conditions of Meniere's disease, more complex of flow characteristic is occurred. This phenomenon presenting high probability of rupture is predicted at the certain area in the anatomy of vestibular system.

The present study deals with the embryonic development of the early and the intermediate embryonic stages of Columba livia domestica inner ear or the membranous labyrinth (10, 15, 20, 22, 26,30,33,36 and 47 mm total body length). During the early development (10 mm stage), neuroepithelium of the ventral rhompencephalon evaginates laterally to form an ectoderm thickening, the otic placode. The latter invaginates forming the otocyst that subsequently gives all other components of the membranous labyrinth. The surrounding mesenchyme is the origin of cartilaginous capsule of the ear. The endolymphatic duct is the first appeared structure in 15 mm stage, followed by cochlear duct (in 22 mm stage) and finally the three semicircular ducts. The latter begin in 26 mm stage and end in 47 mm stage .The inner ear contains sensory organs; the macula of ( utriclus , sacculus) and the crista ampullaris ( of the three semicircular canals ) and the basilar papillae of the cochlear duct; not only for the sense of hearing but also for the equilibrium ,stability and balance. The sensory organs of the intermediate stages (36 and 47 mm stages) showed no differentiation to hair or supporting cells. In the intermediate stage (47 mm stage), the inner ear has undergone a considerable development in its structure. It consists of a dorsal vestibular part including two connecting sacs (utriculus and the sacculus) and three semicircular canals and ventral cochlear part (the cochlear duct). Keywords : Columba, Embryo, Early, Intermediate Stages, Inner Ear Development.

Background: Outcome of endolymphatic sac shunt surgery crucially depends on endolymphatic sac morphology. The intraoperative finding of a fibrotic sac, e.g., will lead to therapy-failure. Aim of the present study was to determine possible developmental changes in endolymphatic sac morphology which could imply, that a shunt operation should not be undertaken in older age. Method: 46 histological temporal bone serial sections were examined. All sections were taken from the Wittmaack Temporal Bone Collection. All specimens were obtained from patients with morphologically healthy ears, especially without a history of Meniere's disease or other kinds of vertigo. Results: During the fetal period the endolymphatic sac is a wide cavity that is surrounded by immature embryonal connective tissue. In older age this cavity gradually shrinks, leading to stenosis in about 80% of the cases. The endolymphatic duct, however, remains open. Conclusion: The increasing fibrosis of the endolymphatic sac is part of the natural involution of the inner ear. It constitutes a natural limitation for the outcome of endolymphatic sac shunt surgery in the elderly.

Na+-K+-2Cl- cotransporter 1 (NKCC1) and c-Jun N-terminal kinase (JNK) were immunohistochemically studied in guinea pig cochlea following the induction of endolymphatic hydrops by blocking the endolymphatic duct. Postoperative survivals were set to 1 day (n=3), 3 days (n=4), 1 week (n=3), 2 weeks (n=4), 1 month (n=4) and 3 months (n=4). The most striking finding was an increase in the immunoreactivity for NKCC1 at type 1 fibrocytes of the spiral ligament throughout the survival times. This suggests that the affected cells shrink as the result of surgical intervention and upregulate NKCC1 to restore the volume of the cells. The shrinkage of type 1 fibrocytes should reduce gap junctional connectivity among cells of the ligament, which could reduce K+ supply into the stria vascularis and disturb ionic homeostasis in the endolymph. On the other hand, JNK, which has been reported to activate NKCC1 by phosphorylation, showed a consistent decrease in immunoreactivity in the types 1 and 2 fibrocytes in hydropic ears, indicating that JNK does not play an important role in the activation of NKCC1 in the cochlea.The findings in the present study suggested that endolymphatic homeostasis depends on cell integrity within the spiral ligament and that NKCC1 in type 1 fibrocytes is crucial in maintaining cochlear fluid homeostasis.

To describe the anatomy of a small network of channels surrounding the human endolymphatic duct.Archival temporal bone sections and a surgical specimen were studied using a variety of techniques.Temporal bone laboratory of the House Research Institute.Archival temporal bone sections were examined by light microscopy, 3D reconstruction, and immunohistochemical labeling. A surgical specimen was examined using electron microscopy. Sections from temporal bones with blocked endolymphatic ducts or amputated sacs were examined for the manifestations of endolymphatic hydrops.Peri-endolymphatic duct channels were found to extend from the proximal cisternal part of the endolymphatic sac to the supporting tissue of the saccule and utricle. Tissue in the channels, as seen by conventional and electron microscopy, is continuous with and identical with the tissue surrounding the endolymphatic duct. Tissue in the channels labels with the S100 antibody similar to the spiral ligament and supporting tissue of the vestibular end organs and suggests a neural crest origin, as did the presence of melanocytes. Obstruction of the endolymphatic duct resulted in endolymphatic hydrops whereas amputation of the sac did not.Endolymph is probably absorbed in the endolymphatic duct. The peri-endolymphatic duct channels that extend from the proximal sac to the supporting tissue of the saccule label with the S100 antibody and contain melanocytes suggest a neural crest origin and involvement in fluid and potassium hydrodynamics similar to those described for the similarly staining spiral ligament of the cochlea.