Sensory cell damage in two-phase endolymphatic hydrops:A morphologic evaluation of a new experimental model by low-voltage scanning techniques

Hypothesis: The aim of this study was to create a more dynamic animal model of Meniere's disease combining multiple causes, such as the role of endocrine factors and endolymphatic sac dysfunction, that may mimic the fluctuant characteristics of Meniere's disease. Background: Endolymphatic hydrops remains to be considered a pathologic substrate in the etiology of Meniere's disease. The classic guinea pig model of inducing hydrops by total destruction of the endolymphatic sac is a nonphysiologic rigid model of Meniere's disease. Methods: The authors developed the two-phase endolymphatic hydrops model by inducing hydrops by mild chronic endolymphatic sac dysfunction, in combination with increased endolymph production by aldosterone. Sensory cell damage was evaluated by low-voltage field emission scanning microscopy. Results: This study describes a wide spectrum of morphologic effects of the outer hair cells in radial gradients, in which most effects were observed in the third to second row of outer hair cells, and longitudinal gradients in which the most severe effects were observed in the apical turns. Most affected were the ears that underwent distal endolymphatic sac dissection followed by the administration of aldosterone. Damaging effects proceeded from degeneration and absence of short stereocilia of outer hair cells and even some inner hair cells in the apical turns, to stereociliary disarrangement and atrophy, followed by degeneration and absence of outer hair cells, which were replaced by supporting cells. Conclusion: The two-phase endolymphatic hydrops model seems to represent a functional model that may mimic the fluctuant characteristics of Meniere's disease and emphasizes the influence of multiple and coexisting hydrops-inducing influences

Two-phase endolymphatic hydrops: A new dynamic guinea pig model

The classical guinea pig model for Meniere's disease, in which endolymphatic hydrops was achieved by destruction of the endolymphatic sac and obliteration of the endolymphatic duct, is a non-physiological profound model with shortcomings in relation to Meniere's disease as seen in patients. We developed a more subtle animal model; the two-phase endolymphatic hydrops. This model is based on a combination of chronic endolymphatic sac dysfunction, induced by slight destruction of the most distal part of the endolymphatic sac, and acute stress-induced endolymph production by stimulation of the Na/K-ATPase in the stria vascularis with aldosterone. Light microscopy of the fluid compartments of four groups of cochleas was used to examine them for the presence of endolymphatic hydrops: i) Normal (control) cochleas showed no hydrops; ii) some of the non-operated (no destruction) aldosterone-treated cochleas showed small degrees of hydrops mainly present in the basal turns; iii) mild dissection of the endolymphatic sac without administration of aldosterone produced a hydrops which was mainly present in the cochlear apex; iv) combination of chronic endolymphatic sac dysfunction and acute attacks of endolymph production by aldosterone administration revealed the most severe degrees of hydrops in ail cochlear windings, damage to cochlear structures, and cellular disturbances of the epithelial lining of the endolymphatic sac. This new model may represent a more physiologic and dynamic approach to Meniere's disease and may explain the etiology of many symptoms in patients such as the fluctuant nature and the types of sensoneurinal hearing losses

Cochlear ultrastructure in two-phase endolymphatic hydrops in the guinea-pig

Endolymphatic hydrops continues to be considered as a pathological factor in the etiology of Meniere's disease. We have developed the two-phase endolymphatic hydrops model, which seems to represent a functional model combining multiple etiologies, and which may resemble the fluctuating characteristics of Meniere's disease. A transmission electron microscopic study was performed on the endolymphatic sacs of four groups of guinea-pig cochleas: (1) controls, (2) non-operated, aldosterone-treated cochleas, (3) operated (dissection of the endolymphatic sac) cochleas, (4) operated and aldosterone-treated cochleas. Light and electron microscopy showed a normal morphology in the controls. Aldosterone as a single treatment resulted in an increased activity of the marginal cells in the stria vascularis. Dissection induced a gradient of degenerative effects and cell loss in the intracellular and extracellular structures of the sensory cells, the stria vascularis and Reissner's membrane, which may be reversible. Subsequent administration of aldosterone induced severe damage and increased cell loss, which may be irreversible. Our findings demonstrate changes that may be reversible due to the compromising effect of a single treatment, and irreversible changes due to interaction of both compromising factors. These findings support our two-phase concept

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 Na/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