Development Of Endolymphatic Hydrops Research Articles

Ischemia of the Endolymphatic Sac

A decrease in vascular density in the endolymphatic sac was suspected as a factor in the pathogenesis of endolymphatic hydrops in Meniere's disease. The present study was undertaken to explore this possibility by cutting the posterior meningeal artery and the sigmoid sinus above and below the external aperture of the vestibular aqueduct or by incision of the dura adjacent to the sinus in 18 guinea pigs. The lesions in the sac were greater in the segmental ablation of the artery and sinus and were consistently associated with the development of endolymphatic hydrops. Among the lesions shown in the sac epithelia, the intermediate portion was most often and most severely affected with a decrease in rugose formation and a flattening of the tall epithelial cells or replacement of epithelial cells by squamous type cells. A high correlation between the lesions in the intermediate portion and occurrence of hydrops suggests that the intermediate portion plays a greater role in the pathogenesis of endolymphatic hydrops. The sac luminal precipitates known to be increased in human Meniere's cases were decreased or absent in this study, which suggests that the increased amount is unlikely to be the cause of endolymphatic hydrops. The evidence supports the hypothesis that these substances are secreted by the endolymphatic sac. The limited sensory cell lesions seen in the cochleae and saccules are likely to be due to a temporary vascular ischemia and endolymphatic hydrops.

内リンパ嚢局所免疫反応による内リンパ水腫の発生機序

Previously the author reported the immediate development of endolymphatic hydrops (e. hydrops) following direct challenge of secondary antigen to the endolymphatic sac (ES) in guinea pigs, during the early phases of postchallenge, ranging from 1 to 5 weeks. The present study reports the results of specimens taken up to 10 weeks postchallenge, and correlation of e.hydrops to perilymph in antigen-specific antibody levels. From the present results, mechanisms of e.hydrops induced ES immune reaction are suggested as follows. 1) In the early stage of e.hydrops, an acute inflammatory reaction in the ES may produce endolymph by an increased vascular permeability of the inner ear and may impair endolymph absorption from the ES. 2) In the latter stage of e.hydrops, the moderate cellular infiltration in the ES may cause chronic impairment of endolymph absorption in the ES.

内リンパ嚢局所二次免疫反応による急性内リンパ水腫 Ｉ： 短期観察

The development of endolymphatic hydrops (e. hydrops) following secondary e. sac immune response was investigated in Hartley guinea pigs, for a period of 5 weeks. E. hydrops immediately developed to a maximum from day 2 to day 7 and then gradually reduced in the next 4 weeks. In the e. sac, numerous inflammatory cellular infiltrates, mainly polymorphonuclear cells and macrophages, were seen from day 1 to day 2. Lymphocytes and plasma cells appeared from day 3 and increased to a maximum by day 7 and then gradually decreased in the next 4 weeks. Neither primary e. sac KLH challenge nor e. sac PBS inoculation could derive e. hydrops. Development of e. hydrops was considerably parallel to the grade of immune reaction within the e. sac, suggesting that immuno-pathological reaction of the e. sac has an important effect on regulation of the endolymph volume.

The surgical approach to the endolymphatic sac and the cochlear aqueduct in the guinea pig

The endolymphatic sac and cochlear aqueduct are primary passages of the endolymphatic and perilymphatic fluid compartments in the labyrinth. Closure of the endolymphatic sac and duct in the guinea pig will result in the development of endolymphatic hydrops. Although obstruction of the cochlear aqueduct in this species does not seem to result in any dysfunction, this structure may serve in the dynamics of inner ear fluid physiology. The anatomy of the guinea pig temporal bone is described with special emphasis on the endolymphatic sac and cochlear aqueduct. Surgical techniques to gain access to these structures through both a middle and posterior cranial fossa approach are described.

The development of endolymphatic hydrops following CMV inoculation of the endolymphatic sac.

The effect of inoculation of cytomegalovirus (CMV) into the endolymphatic sac was examined in CMV-seronegative and seropositive animals. Seronegative animals developed hearing loss, infection in the epithelial cells of the endolymphatic sac and perisaccular connective tissue, and endolymphatic hydrops. Control animals inoculated with inactivated CMV showed no hearing loss, viral infection, or endolymphatic hydrops. Seropositive animals showed complete protection from hearing loss and viral infection, yet a monocytic infiltrate was seen surrounding the endolymphatic sac. Associated with this localized immune response was mild evidence of endolymphatic hydrops in 40% (2/5) of the animals. Control seropositive animals inoculated with inactivated CMV showed no hearing loss or morphological changes. CMV then, can infect cells of the endolymphatic sac resulting in hearing loss and endolymphatic hydrops. The immune response to CMV in seropositive animals is protective, but is associated with endolymphatic sac inflammation.

Physiological Change in the Endolymphatic Space During the Development of Endolymphatic Hydrops

The purpose of this experiment was to clarify the pattern of physiological change in the inner ear during the development of endolymphatic hydrops. Endolymphatic hydrops was experimentally induced in 67 guinea pigs by the introduction of silver nitrate into the endolymphatic sacs. The animals were sacrificed 1 day to 6 weeks later, and HE stained serial sections were made of their temporal bones. The endolymphatic spaces were examined under a light microscope and measured by computer to determine the pattern of size changes. The results were as follows :1) The saccule displayed the greatest degree of hydrops, with the saccules of the treated guinea pigs dilating to 7 times the size of the saccules in the control group.2) Cochlear hydrops developed principally in the upper turns during the first 3 weeks, and in the lower turns during the second 3 weeks. The final result was an even degree of dilation throughout the cochlea to a size 2.5 times normal.3) The utricle, which had been thought to display minimal dilatation, showed nearly the same degree of bulging as the cochlea : 2.5 times normal at 6 weeks.

Evolution of recruitment at different frequencies during the development of endolymphatic hydrops in the guinea pig.

The study of human temporal bones has identified endolymphatic hydrops as a common feature of several diseases. In particular it is systematically found in those bones removed from patients with premortem Menière's disease. Menière's disease is known to induce sensorineural pathology with recruitment, which changes with the evolution of the hearing loss, and is suspected to induce a cochlear conductive loss by a possible increase in static pressure of endolymph. Amplitude/intensity functions of sensorineural responses can reflect recruitment and/or conduction loss. Experimentally induced hydrops in animals provokes cochlear physiological alterations, some of which closely resemble certain features of Menière's disease. In the present study using a guinea-pig animal model, we have examined amplitude/intensity functions at the round window for cochlear microphonics (RWCM), summating potentials (RWSP) and action potentials (CAP) at different stages of hearing loss in experimentally induced hydrops. During the period of fluctuating thresholds there was reduction of maximal RWCM amplitude, no change in RWSP and recruitment on the CAP. At a later stage when the audiogram was flat and fluctuations were no longer seen, RWCM remained unchanged. At this time RWSP could show recruitment while CAP amplitudes at all intensities were reduced, indicating either a cochlear conductive loss and/or a general depression of neural activity.

Function of the Stria Vascularis in Endolymphatic Hydrops

We examined electronmicroscopically the inner ear of guinea pigs sensitized with the stria vascularis of rabbits. 25, 000 units of HRP were injected through a catheter in the right jugular vein. The tracer was observed in the stria vascularis, around the capillary vessels, in the marginal cells and in the intercellular spaces of these animals. The region of the intermediate cells in the stria vascularis was stained with HRP, and vacuolar degeneration was present in the marginal cells. This implies that the parenchymatous cells of the stria vascularis are damaged. We examined the effect of anaphylatoxins on the stria vascularis.Ten guinea pigs were injected with Zymosan+guinea pig serum+e-aminocaproic acid and 10 guinea pigs with guinea pig serum+e-aminocaproic acid into the carotid artery. Under anesthesia with nembutal, these animals were perfused with 10% neutral formalin and immobilized. Tissues were examined after HE staining. The stria vascularis of various cochlear turns showed marked atrophy except in the basal turn, and also some animals indicated the mild endolymphatic hydrops. These findings suggest that endolymphatic hydrops and other inner ear pathological conditions are related to anaphylotoxins.Furthermore, electronmicroscopic findings included hyperpermeability of the stria vascularis. The increase of permeability may be due to the leakage in intercellular spaces or in the destroyed region of the endothelial cells in addition to the usual vesicular transport.We conclude that the stria vascularis plays an important role in the development of endolymphatic hydrops.

The effect of kanamycin on experimentally induced endolymphatic hydrops.

In guinea pigs with endolymphatic hydrops 6 months after operation the DC potential had decreased from +80 mV to +50 mV, while the sodium activity had increased. The twofold increase in Na+ activity could explain the increased degree of endolymphatic hydrops. The K+ activity and Cl- activity were unchanged. However, endolymphatic hydrops could be produced in kanamycin-induced deaf guinea pigs after obliteration of the endolymphatic sac and duct. The physiological data on DC potential, K+, and Na+ activity were similar to those for non-treated animals. When the animals were treated with kanamycin 6 months after the development of endolymphatic hydrops, there was no effect on the morphological and functional changes compared to controls. The data suggest that regulation of the inner ear fluid occurs independent of an intact auditory system. The effect of aminoglycoside treatment in Ménière's disease cannot be explained by an effect on endolymphatic hydrops formation.

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.

DC potential and K+ activity in experimental endolymphatic hydrops.

No alteration in K+ activity of endolymph and perilymph was seen during development of endolymphatic hydrops in guinea pigs. The DC-potential was not changed during enlargement of endolymphatic space.