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Osmotically induced macrophage activity in the endolymphatic sac. On the possible interaction between periaqueductal bone marrow cells and the endolymphatic sac.

This study aimed to investigate the origin of the free cells in the lumen of the endolymphatic sac (ES). Activation of the cells was accomplished through osmotic induction using glycerol. The ES and the perisaccular tissue were analyzed with special reference to the activity of periaqueductal bone marrow cells after different time intervals following the injection of hyperosmotic agents. The results show that the perisaccular or periaqueductal bone marrow space may constitute a source of some of the free cells occurring in the ES. Osmotic challenging of the inner ear may cause activation of the periaqueductal bone marrow, initiating the locomotion and migration of cells (mostly monocytes, neutrophils and eosinophilic leukocytes) along bone marrow sinusoids that frequently anastomose with the ES vessels. The free cells show signs of transepithelial diapedesis and, in the lumen of the ES, cells may develop into phagocytes which initiate the ingestion and degradation of secreted macromolecular aggregates. It is thought that osmotic alterations in the inner ear may give rise to local changes in or around the ES, leading to the chemotactic attraction of bone marrow cells. The results verify the existence of a complex sugar/protein aggregate metabolism over the wall of the ES, which is linked to the turnover of free cells. The findings may indicate that ES macrophages are important in the regulation of inner ear fluid homeostasis.

Animals↗

Ultrastructure of the endolymphatic sac in two-phase endolymphatic hydrops in the guinea pig.

Two-phase endolymphatic hydrops is a subtle experimental model for Meniere's disease. Chronic dysfunction of the endolymphatic sac, induced by dissection of the most distal part without causing damage to the intermediate part, is combined with increased endolymph production induced by administration of aldosterone which stimulates the N/K-ATPase in the stria vascularis. A transmission electron microscopic study was performed on the endolymphatic sacs of four groups of guinea pig cochleas: controls: non-operated aldosterone-treated cochleas; operated (dissection of the endolymphatic sac) cochleas; operated and aldosterone-treated cochleas. Light and electron microscopy showed a normal morphology in the controls. Aldosterone treatment had no visible effect. Dissected ears revealed severe deviations. The epithelium of the intermediate sac was low, showed dilated lateral intercellular spaces indicating elevated fluid transport and displayed serious degenerative processes. Distally, the endolymphatic sac was completely blocked by newly formed bone. Additional aldosterone treatment had no cumulative effect on the dissected ears.

Aldosterone↗

The surgical anatomy of the endolymphatic sac.

The endolymphatic sac (ELS) and vestibular aqueduct (VA), which play a notable role in the pathogenesis of endolymphatic hydrops and Meniere disease, were identified in all anatomic and tomographic materials. More than 100 temporal bones were used for microdissection, tomography, and plastic molds. Normal subjects and Meniere disease patients were studied tomographically (N = 63) and observed during ELS surgery (N=49). In Meniere disease there is, with increassing duration of diseases, a decrease in the periaqueductal and opercular air cell pneumatization, with a concomitant shorter and straighter VA. This correlates with a decreased ELS luminal patency, and a more inferiorly positioned ELS. These factors help to explain both the difficulties of visualizing the VA by tomography in Meniere disease as well as the occasional difficulties reported by others in satisfactorily identifying the ELS at sac surgery. All observations are made from the surgeon's viewpoint to enhance clinical identification of the ELS.

Adult↗

The non-specific effect of endolymphatic sac surgery in treatment of Meniere's disease: a prospective, randomized controlled study comparing "classic" endolymphatic sac surgery with the insertion of a ventilating tube in the tympanic membrane.

A prospective, randomized study was carried out comparing the effect of two surgical modalities in the treatment of patients with Meniere's disease: insertion of an endolymphatic sac shunt and insertion of a ventilating tube in the tympanic membrane. A total of 29 patients, 12 males and 17 females, age 27-71 years, were operated on in two ear, nose and throat (ENT) departments. Of these patients, 15 had an endolymphatic shunt inserted and 14 had a ventilating tube inserted in the tympanic membrane. Postoperative follow-up was carried out in the department in which the patients had not been operated. The severity of the disease was scored pre- and postoperatively, and the results evaluated under the guidelines of the Committee on Hearing and Equilibrium (1995) for the diagnosis and evaluation of therapy in Meniere's disease. The patients in both groups had a statistically significant reduction in dizzy spells, measured 6 and 12 months postoperatively, and there was no difference between the groups. The pathophysiological explanation for the reduction in dizzy spells in each of the treatment modalities is debatable and the effect is non-specific. The patients' hearing and tinnitus were statistically unaffected by the treatment in both groups, though 2 patients in the shunt group developed severe hearing loss (anacusis/70 dB).

Adult↗

[Clinical relevance of developmental changes of the endolymphatic sac].

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 Menière'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.

Adolescent↗

Functional and morphological findings of endolymphatic sac.

After obliteration of endolymphatic sac and duct, no significant alteration in d.c. potential, K+ activity or protein content during the development of endolymphatic hydrops could be observed. The K+ activity of endolymphatic sac was only one-ninth of that in the cochlear part of the endolymph. After injection of Thorotrast into the endolymphatic sac, aggregated particles were found in the cochlear endolymph 2 days later. Ethacrynic acid (60 mg/kg) caused a decrease in K+ activity in the cochlear endolymph, but an increase in the endolymphatic sac. Intercellular edema was observed both in stria vascularis and in endolymphatic sac by light and electronmicroscopy after ethacrynic acid administration. These results suggest the existence of an active transport mechanism in the endolymphatic sac epithelium.

Animals↗

Lymphocyte-macrophage activity in the human endolymphatic sac.

The human endolymphatic sac was analysed electron microscopically in patients undergoing acoustic Schwannoma surgery or vestibular nerve section. In addition, endolymphatic sacs from cadavers were analysed light microscopically. The results show that the human sac is endowed with a variable number of leucocytes and that there is a continuous recirculation of immuno-competent cells in this area of the inner ear that may be of importance for clearance of the inner ear from foreign substances and microorganisms derived from nearby located infection-prone areas. The possibility in Meniere's disease of a disturbed immunological activity in the sac is discussed.

Ear, Inner↗

Innervation of the endolymphatic sac.

Previous studies suggest that the endolymphatic sac plays an important role in the homeostasis of endolymph. Factors that influence blood flow in the sac may affect its function. This blood flow may be influenced by autonomic innervation; however, no such innervation has been demonstrated. The purpose of this study was to demonstrate catecholaminergic and cholinergic fibers on the endolymphatic sac. Endolymphatic sacs from Hartley guinea pigs were stained either immunocytochemically for tyrosine hydroxylase to reveal catecholaminergic fibers or histochemically for acetylcholinesterase to reveal cholinergic fibers. For tyrosine hydroxylase immunostaining, the endolymphatic sacs were treated with dilute hydrogen peroxide and then incubated in the primary antiserum. The tissue was further processed by the avidin-biotin immunoperoxidase method and reacted with diaminobenzidine. For acetylcholinesterase histochemistry, the tissue was processed by a modification of the direct thiocholine method. Light microscopy of the whole-mounted endolymphatic sacs revealed tyrosine hydroxylase-positive and acetylcholinesterase-positive fibers. Some of the acetylcholinesterase-positive fibers were clearly associated with vessels. This innervation, which has not been described previously, may significantly influence blood flow and function of the endolymphatic sac.

Acetylcholinesterase↗

The endolymphatic sac: microsurgical topographic anatomy.

The endolymphatic sac is part of the membranous labyrinth; it plays an important role in the hearing mechanism. Injury to the endolymphatic sac may, over time, severely compromise hearing. The endolymphatic sac is located in a duplication of the dura of the posterior aspect of the petrous pyramid and is, therefore, in the surgical field of many neurosurgical operations performed on the posterolateral cranial base. The endolymphatic sac was exposed bilaterally in 10 anatomic specimens; the distance from the center of the sac to the posterior lip of the internal auditory meatus and to the XIth nerve in the jugular foramen was measured with a caliper. Also measured was the distance between the center of the sac and the closest point on the petrous ridge and the distance between that point and the petro-sigmoid intersection. The petro-sigmoid intersection was defined as the point at which the medial aspect of the sigmoid sinus intersects the lateral aspect of the petrous ridge. The dimensions of the sac were also recorded. On the average, the sac was found to be 15.7 mm posterosuperior (superolateral) to the XIth nerve in the jugular foramen (range, 11.0-18.5 mm) and 13.3 mm posterior (lateral) to the internal auditory meatus (range, 10.0-18.0 mm). The center of the sac was 24.1 mm (mean value) (range, 20.0-28.0 mm) in front of the petro-sigmoid intersection at a point 11.5 mm (mean value) (range, 8-17 mm) below the petrous ridge. The mean width and height of the sac were 3.83 (range, 2-6 mm) and 3.80 mm (range, 2.5-8 mm), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anatomy, Artistic↗

In vitro fluid and particle transport in the murine endolymphatic sac.

The murine endolymphatic sac (ELS) can survive for several weeks in tissue culture. The epithelial cells mature in vitro and demonstrate functional activity under these artificial conditions. The goal of the present study was to investigate fluid and particle transport between the ELS cells, the ELS lumen, and the surrounding tissue culture medium. A series of tracers, including anti-mouse IgG-labelled colloidal gold, horseradish peroxidase (HRP), and ruthenium red (RR) were used to elucidate different aspects of ELS transport. Results indicated that both light and dark cells of the ELS took up HRP from both the luminal and the basal side of the epithelial cells, forming coated vesicles. Only luminal uptake occurred when the HRP was injected into the lumen, and only basal uptake was observed when the HRP was placed in the culture media. HRP introduced into the tissue culture media never entered the lumen of the ELS. Anti-mouse IgG labelled with gold showed no uptake at all from either side of the epithelial cells. Gold could be found only in membrane-bound vesicles in the cytoplasm of reticuloendothelial (RES) cells in the ELS lumen and lateral intercellular spaces (LIS) of the sac. This suggests that there are no IgG sites in sac cells and that the circulating RES cells seen in the lumen of the ELS come from the surrounding connective tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in hyaluronan synthesis by in vitro cultured endolymphatic sac cells.

The endolymphatic sac (ELS) has been implicated in the maintenance of endolymph volume and pressure in the membranous labyrinth through fluid resorption and secretion of osmotically active substances, known as glycosaminoglycans (GAGs). To assess whether the ELS cells synthesize the GAG, hyaluronan (HA), and to further elucidate the secretory function of the ELS, a series of experiments were carried out on in vitro tissue-cultured, fetal murine ELSs. In phase 1 of the investigation, the ELSs that were attached to a small portion of the posterior labyrinth, were resected from whole otocyst specimens and studied in tissue culture. This model was chosen to determine whether a change in endolymph homeostasis affects ELS activity. Radiolabeled 14C glucose incorporation was used to evaluate HA synthesis by ELS cells when cultured in vitro. Approximately 43 percent of the incorporated 14C glucose radiolabel was digested by Streptomyces hyaluronidase (an HA-specific hyaluronidase), suggesting HA synthesis by sac cells. In phase 2 of our experiments, the ELSs were not resected from the otocysts. Instead, they were left attached to intact membranous labyrinths, and whole otocysts were cultured. Studies analogous to those of phase 1, assessing the ability of the ELS cells to incorporate 14C glucose into HA, were performed on these specimens. Streptomyces hyaluronidase treatment of these ELS specimens resulted in a reduction in the removal of radiolabel. Therefore, the ELS cells of intact otocysts incorporated less 14C glucose into HA when compared to the ELS cells of the resected specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A subpopulation of Menière's patients produce antibodies that bind to endolymphatic sac antigens.

The endolymphatic sac (ES) has been suggested to serve an important immunological role within the inner ear. Meanwhile, immunological mechanisms have been studied in connection with Meniere's disease. The aim of this study is to look for and recognize antibodies against the ES in the sera of patients with Meniere's disease, using the technique of indirect immunofluorescence. Sera from 50 patients with Meniere's disease, from an animal model of autoimmune inner ear disease, and from healthy controls were tested against ES tissue substrates obtained from guinea pigs. Immunoglobulin deposition in the ES was found in 20 patients (40%) compared with one control (10%). The difference was statistically significant when computing the odds ratios at 95% confidence level. Fluorescein labeling was demonstrated in the ES epithelium in 16% and in the surrounding perisaccular stroma in 24%. Identical immunoreactivity against the ES tissue was depicted in the sera of the experimental animal model. These findings support the possibility of humoral immunological involvement in the Meniere's disease process. Immunological derangement of the ES function could be the first step in a cascade of reactions leading to endolymphatic hydrops and presenting as Meniere's disease.

Antibody Formation↗

Effects of hyperosmolar substances on the endolymphatic sac.

The murine endolymphatic sac (ES) was studied 15 min to 8 hours after intravenous glycerol administration. Initially the ES showed varying degrees of obliteration and this was mostly pronounced at 15-60 min after the injection. After 2 hours the normal volume was regained and after 4 hours the lumen was dilated to 160% of its normal volume. After 6-8 hours the ES had almost regained its normal appearance. The epithelial lining showed an increase in the number of granular cells which, after two hours, reached a peak of 15.8% (p less than 0.01) compared to normal controls which showed 6.1% granular cells of total cell population in the ES. The increase of granular cells was accompanied by filling of the ES lumen with a stainable substance. The epithelial reaction may serve the purpose of counteracting decreases in endolymph pressure either in the ES or in the entire labyrinth.

Animals↗

Hyaluronan synthesis by in vitro cultured endolymphatic sac cells.

The endolymphatic sac (ELS) has been the subject of investigation for many years and yet its overall function remains unclear. It is believed mainly to be involved in the regulation of endolymph through fluid resorption and secretion of osmotically active substances. The present study was performed using in vitro cultured, fetal ELSs of 18 to 19 day gestational mice, to assess whether the ELS cells can synthesize the osmotically active polysaccharide, hyaluronan (HA). The ELS and portions of the membranous labyrinth were dissected from whole otocyst specimens and placed in 14C glucose-enhanced tissue culture media. A light microscopic (LM), autoradiographic study was performed to assess whether 14C glucose could be incorporated by the tissue into HA. Both the ELS cells and the adjacent cartilage demonstrated radiolabel incorporation within 4 hours of incubation in tissue culture medium, with increased radiolabel density in ELS cells after 24 hours of incubation. HA-specific hyaluronidase (HAase) resulted in removal of HAase-sensitive compounds in the ELS in both 4-hour and 24-hour cultured specimens when compared to adjacent cartilage cells (p = 0.001). Approximately 43 percent of the radiolabel was incorporated into HA in ELS specimens, as compared to a 22 percent HA synthesis in the adjacent cartilage tissue, suggesting preferential synthesis by ELS cells. The dissected murine otocysts demonstrate viability in vitro as measured by their ability to incorporate 14C glucose from tissue culture medium. Under these conditions the cultured ELS demonstrates an ability to synthesize HA. A theory of ELS function is proposed.

Animals↗

[Immunohistochemical study of the endolymphatic hydrops due to secondary endolymphatic sac immune reaction].

Secondary endolymphatic sac (ES) immune response against keyhole limpet hemocyanin (KLH) were immunohistochemically investigated in guinea pigs by analysing the distribution of IgG and C3 complement in the inner ear over a 4-week period. After systemic sensitization with KLH and Freund's adjuvant, KLH was inoculated into the right ES by trans-cranial approach. KLH was found in the ES immediately after KLH challenge and then disappeared on the 7th day. On the 2nd and 3rd day moderate endolymphatic hydrops and a massive cell infiltrations within the ES were observed, and they gradually decreased their severity with time. Diffuse stainings with IgG and C3 were found in the ES, the epithelial and subepithelial regions of the vestibule. Similar findings were obtained in the spiral ligament and the hair cells after antigen challenge. IgG bearing cells were detected within the endolymphatic sac alone. Our results suggested that endolymphatic hydrops may be produced by the imbalance of in-out flow of the endolymph and the immunologically mediated inflammation through IgG-complement system.

Animals↗

Postnasal maturation of the human endolymphatic sac.

OBJECTIVE/HYPOTHESIS: The objective of this study was to trace the postnatal development of the human endolymphatic sac. The endolymphatic sac starts as a pouch-like structure during the fetal period in the human but later develops into a complex network of tubules in its mature form. STUDY DESIGN: Observational study. METHODS: Light microscopic examination of the morphology of the endolymphatic sac in a population of temporal bones. RESULTS: Examination of 28 temporal bones from 19 infants and children reveals that endolymphatic sac morphological maturation is usually completed in the first year of life, although it may occur as late as 4 years of age. There was good correlation of maturation levels between sides when pairs of temporal bones were evaluated. Immature pouch-like endolymphatic sacs may appear as late as 4 years of age. CONCLUSIONS: Endolymphatic sac maturation to its adult tubular form is usually completed by the first year. This finding contrasts with other studies examining the growth of the endolymphatic sac to adult size after birth. Histological evidence suggests that the endolymphatic sac, although not morphologically mature by appearance, may still be participating at some level of functioning.

Child, Preschool↗

[Surgery of the endolymphatic sac and preservation of hearing in endolymphatic hydrops].

Vertigo is the most important symptom of Ménière's disease both from the standpoint of follow-up and indication for surgery. But although vertigo is an alerting symptom for both the patient and the physician, we believe that the hearing level is the most reliable and even the single sign in determining the recent status of the disease. Between 1983-1989, 42 patients with various types of Ménière's disease (MD) (34 typical MD, 3 cochlear MD and 3 vestibular MD) underwent endolymphatic sac surgery at ENT department of Gazi University School of Medicine. In the typical MD group, patients with a duration of symptoms of less than one year prior to surgery revealed better postoperative results; 91% fell into class A and B, whereas this rate was found to be lower (40%) in patients with symptomatology lasting for more than one year. In conclusion, especially in bilateral cases, given the importance of the hearing, early sac surgery is thoroughly recommended for the conservation of hearing.

Adult↗