Experimental Endolymphatic Hydrops Research Articles

МОРФОЛОГИЧЕСКИЕ ИЗМЕНЕНИЯ В СОСУДИСТОЙ ПОЛОСКЕ ПРИ ЭКСПЕРИМЕНТАЛЬНОМ ЭНДОЛИМФАТИЧЕСКОМ ГИДРОПСЕ

Abstract. Introduction. Etiopathogenesis of Ménière’s disease is still poorly understood, although the morphological substrate of this disease is known well: It is endolymphatic hydrops. Animal modeling of endolymphatic hydrops has traditionally been used to study the relationship between hydrops and changes in the inner ear. In recent years, the attention of researchers has been attracted by microcirculatory disorders in the stria vascularis during experimental endolymphatic hydrops, since the stria vascularis is essential to maintaining endolymph homeostasis, transporting ions, generating endocochlear potential, and supporting the function of the organ of Corti. Aim. This study was aimed at examining alterations in the stria vascularis in experimental endolymphatic hydrops. Materials and Methods. Endolymphatic hydrops was modeled in 90 rats by irrigating the lateral surface of the neck in the projection of the vertebral artery with chloroethyl to simulate vasomotor disorders. Animals were killed at different periods after exposure (1-8 days). In the 1st series of experiments (40 animals), we studied the dynamics of pathomorphological changes in the cochlea, while in the 2nd series (40 animals), we studied changes in the stria vascularis after intravital isolation of the cochlea. Results and Discussion. Local cooling of the lateral surface of the neck of rats led to forming the labyrinth hydrops on the affected side with the key morphological features: Edema of cellular elements, deformation of membranes (vestibular and tectorial), and vascular disorders (hyperemia of the vascular stria, venous congestion). Hydropic changes reached their maximum on the 4th day after exposure. In the capillaries of the stria vascularis, we observed an expansion of their diameters, sludge syndrome, and the edema of paravascular tissues. Microcirculatory changes correlated with the severity of EG signs, reaching their maximum on the 4th day after exposure with subsequent regression. Conclusions. Synchronous development of microcirculatory and hydropic changes in the inner ear indicates that the vascular factor is involved in forming the experimental endolymphatic hydrops.

A Revised Surgical Approach to Induce Endolymphatic Hydrops in the Guinea Pig.

Endolymphatic hydrops is an enlargement of scala media that is most often associated with Meniere's disease, though the pathophysiologic mechanism(s) remain unclear. In order to adequately study the attributes of endolymphatic hydrops, such as the origins of low-frequency hearing loss, a reliable model is needed. The guinea pig is agood model because it hears in the low-frequency regions that are putatively affected by endolymphatic hydrops. Previous research has demonstrated that endolymphatic hydrops can be induced surgically via intradural or extradural approaches that involve drilling on the endolymphatic duct and sac. However, whether it was possible to create an endolymphatic hydrops model using an extradural approach that avoided dangerous drilling on the endolymphatic duct and sac was unknown. The objective of this study was to demonstrate a revised extradural approach to induce experimental endolymphatic hydrops at 30 days post-operatively by obliterating the endolymphatic sac and injuring the endolymphatic duct with a fine pick. The sample size consisted of seven guinea pigs. Functional measurements of hearing were made and temporal bones were subsequently harvested for histologic analysis. The approach had a success rate of 86% in achieving endolymphatic hydrops. The risk of cerebrospinal fluid leak was minimal. No perioperative deaths or injuries to the posterior semicircular canal occurred in the sample. The presented method demonstrates a safe and reliable way to induce endolymphatic hydrops at a relatively quick time point of 30 days. The clinical implications are that the presented method provides a reliable model to further explore the origins of low-frequency hearing loss that can be associated endolymphatic hydrops.

Standardized surgical approaches to ear surgery in rats

ObjectiveTo describe several approaches of ear surgeries for experimental studies in rats. MethodsAnesthetized rats were prepared for demonstration of various ear surgery approaches designed to optimize experimental outcomes in studies with specific goals and exposure requirements. The surgical approaches included the posterior tympanum, superior tympanum, inferior tympanum and occipital approaches. ResultsThe middle ear cavity and inner ear were successfully exposed from different angles via the mentioned surgical approaches. For example, electrode placement for recording of cochlear bioelectric responses was easily achieved through the posterior tympanum or inferior tympanum approach. Alternatively, drug delivery or gene transfection via round window membrane was most easily accomplished using the posterior tympanum approach. Cochlear perfusion of protective or ototoxic drugs was best performed using the inferior tympanum approach. Ossicular chain interruption to induce a prolonged conductive hearing loss was readily achieved using a superior tympanum approach. Lastly, surgical destruction of the endolymphatic sac to induce experimental endolymphatic hydrops was readily performed via an occipital surgical approach. ConclusionThese standardized surgical approaches can be applied in scientific studies of the ear with different purposes covering electrophysiology, conductive hearing loss, intra-cochlear drug perfusion and experimental studies relevant to Meniere's disease.

B106 Identification of factors which promote hearing preservation

The aim of this study was to investigate the audiological and histopathologic effects of dexamethasone in the treatment of experimentally induced endolymphatic hydrops.Thirty mature, male guinea pigs weighing 400 ± 50 g were operated on to induce experimental endolymphatic hydrops in their right ear. Left ear served as control. Subjects were separated into control and dexamethasone groups, with the latter receiving dexamethasone 5 mg/(kg d) intraperitoneally for 10 days. Electrocochleography and auditory brainstem response were applied to all subjects at preoperation, on the second postoperative day and also on the 15th postoperative day in animals that lived for a long time. The histopathologic examination of the inner ear in all animals was done at the end of the study.The summating potential and the ratio of the summating potential to the action potential measured on the second postoperative day were found to be increased in both groups, but more significantly in the control one. When the left and right ears were compared, significant difference was found in the control group; however, no significant difference was found between the ears in the dexamethasone group. Histopathologic examination revealed varying degrees of hydrops in the control group, but showed only normal findings or minor changes in the dexamethasone group.Dexamethasone can prevent the audiological and histopathologic findings of experimentally induced endolymphatic hydrops. However, these results must be supported by clinical and experimental studies designed with a large number of subjects.

Time Course of Vestibular Function Changes of Experimental Endolymphatic Hydrops in Guinea Pigs

Objective: To investigate the relationship between endolymphatic hydrops and vestibular dysfunction. Methods: 20 pigmented guinea pigs were used: 15 for a hydrops group and 5 for a sham group. Endolymphatic hydrops was produced by electrocauterization of the endolymphatic sac on the left ears. In the horizontal vestibuloocular reflex (HVOR) study, HVOR responses were recorded before and 1, 2, and 4 weeks after surgery in 9 animals of the hydrops group and 5 animals of the sham group. HVOR gain under sinusoidal rotation with a maximal head velocity of 45°/s and frequencies of 0.05, 0.1, 0.2, 0.4 and 0.8 Hz was analyzed. In the nystagmus study, spontaneous nystagmus was recorded in all animals of the hydrops and the sham groups for 1 h in the dark and the maximum slow-phase velocity was measured before and 1, 2, 4 weeks after surgery. Morphological changes in the inner ear were measured light microscopically. Results: In the hydrops group, the HVOR gains at all stimulation frequencies seemed to decrease 1 week after surgery and recover 2 or 4 weeks after surgery; however, there were no statistical differences among HVOR gains in any periods after surgery. The incidence of spontaneous nystagmus gradually increased after surgery and the direction and onset showed large variation. The duration of nystagmus was approximately 10 min. The degree of endolymphatic hydrops showed large variation. In the sham group, HVOR gains at all stimulation frequencies showed no statistically different change in any period after surgery. In the sham group, no animal showed spontaneous nystagmus. Conclusion: Experimentally induced endolymphatic hydrops seems to contribute to vestibular dysfunction to some extent. We speculated that when endolymphatic hydrops is progressing, vestibular dysfunction might occur.

Spiral ganglion loss outpaces inner hair cell loss in endolymphatic hydrops

Neuronal toxicity is thought to be important in Meniere's disease and experimental endolymphatic hydrops (ELH). This study quantifies the relationship between neuronal degeneration and hair cell degeneration in ELH to evaluate the hypothesis that a primary neural insult would yield greater loss in the spiral ganglion than at the inner hair cell level. Following induction and histopathologic confirmation of endolymphatic hydrops in guinea pigs, the degree of hydrops, spiral ganglion loss, and hair cell degeneration were quantified and compared. Guinea pigs with surgically induced unilateral hydrops were sacrificed and their cochleas preserved. Hydrops severity and spiral ganglion density were quantified using automated methods. Hair cells were counted manually. Values were normalized against the contralateral ear to create loss indexes. Inner hair cell (IHC) loss at the apex is significantly lower than corresponding neuronal loss. IHC loss at the base is also lower than neuron loss, although not significantly. Regression analysis shows a significant, positive correlation between neuron loss severity and IHC loss severity at the apex, but not at the base. There is no correlation between hydrops severity and inner hair cell loss. By confirming that spiral ganglion loss is more severe than hair cell loss, and that hair cell loss appears to worsen with neuronal degeneration, this study supports the theory that neuronal toxicity is the primary insult in ELH-related disorders, such as Meniere's disease, and may provide the basis for designing treatment strategies.

Chronological changes in the eighth cranial nerve compound action potential (CAP) in experimental endolymphatic hydrops: the effects of altering the polarity of click sounds

Conclusion: Using a guinea pig model of experimental endolymphatic hydrops, click sounds of altered polarity showed different latencies and amplitudes in hydropic compared with normal cochleae. Latency changes appeared as early as 1 week after endolymphatic obstruction. This method can help diagnose endolymphatic hydrops. Objective: The goal of the study was to develop an objective electrophysiological diagnosis of endolymphatic hydrops. Materials and methods: Endolymphatic hydrops were created surgically in guinea pigs. The latency and the amplitude of the eighth cranial nerve compound action potential (CAP) for click sounds of altered polarity were measured up to 8 weeks after the surgery. Results: At early stages after surgery, the latency for condensation clicks became longer, and at later stages the latencies for both condensation and rarefaction became longer. The discrepancy in the latencies for rarefaction and condensation click sounds (rarefaction minus condensation) became larger by the first week after surgery, but no further discrepancy occurred thereafter. Compared with latency changes, amplitude changes in the CAP were rapid and progressive following surgery, suggesting ongoing damage to hair cells.

Evaluation of the effect of dexamethasone in experimentally induced endolymphatic hydrops in guinea pigs

Purpose The aim of this study was to investigate the audiological and histopathologic effects of dexamethasone in the treatment of experimentally induced endolymphatic hydrops. Materials and methods Thirty mature, male guinea pigs weighing 400 ± 50 g were operated on to induce experimental endolymphatic hydrops in their right ear. Left ear served as control. Subjects were separated into control and dexamethasone groups, with the latter receiving dexamethasone 5 mg/(kg d) intraperitoneally for 10 days. Electrocochleography and auditory brainstem response were applied to all subjects at preoperation, on the second postoperative day and also on the 15th postoperative day in animals that lived for a long time. The histopathologic examination of the inner ear in all animals was done at the end of the study. Results The summating potential and the ratio of the summating potential to the action potential measured on the second postoperative day were found to be increased in both groups, but more significantly in the control one. When the left and right ears were compared, significant difference was found in the control group; however, no significant difference was found between the ears in the dexamethasone group. Histopathologic examination revealed varying degrees of hydrops in the control group, but showed only normal findings or minor changes in the dexamethasone group. Conclusions Dexamethasone can prevent the audiological and histopathologic findings of experimentally induced endolymphatic hydrops. However, these results must be supported by clinical and experimental studies designed with a large number of subjects.

Effects of a Nitric Oxide Synthase Type II Inhibitor on Compound Action Potential Thresholds in Experimental Endolymphatic Hydrops

Nitric oxide (NO) is likely to be synthesized by nitric oxide synthase Type II (NOS II) action and may partake in the origin of changes of compound action potential (CAP) threshold observed in guinea pigs with induced endolymphatic hydrops. This study aimed to assess the action of a NOS II inhibitor on CAP thresholds in these experimental samples. In guinea pigs with experimental endolymphatic hydrops, there are lesions on the cochlea and progressive increase of CAP threshold. NOS II was found in the cochlea of this animal model, and it was inferred that NO can contribute by such alterations. The animals were divided into two groups, in which eight received an intake of a NOS II inhibitor, aminoguanidine, and another eight served as a control group. During 16 weeks, CAP thresholds at 1,000, 2,000, 4,000 and 6,000 on electrocochleography were compared between the groups. The group that had an intake of aminoguanidine showed a lower increase on CAP thresholds at 2,000 (p < 0.05) and 6,000 Hz (p < 0.05) at the 12th postoperative week, and at 1,000 (p < 0.05), 2,000 (p < 0.001), 4,000 (p < 0.001), > and 6,000 Hz (p < 0.001) at the 16th week. We conclude that NOS II inhibitor reduced the elevation of CAP thresholds in experimentally induced endolymphatic hydrops.

Hidropsia endolinfática experimental sob ação de inibidor da óxido nítrico sintase tipo II: avaliação com emissões otoacústicas e eletrococleografia

No modelo experimental de hidropsia endolinfática há redução na amplitude das emissões otoacústicas produtos de distorção (EOAPD) e elevação nos limiares eletrofisiológicos na eletrococleografia. Estudos mostraram que há expressão da óxido nítrico sintase tipo II (ONS II) na cóclea com hidropsia, sugerindo a participação do óxido nítrico (ON) na patogênese desta doença. O objetivo deste trabalho foi avaliar a ação de um inibidor da ONS II nas EOAPD e eletrococleografia em cobaias com hidropisia endolinfática experimental. MATERIAL E MÉTODOS: Foram estudadas 16 cobaias nas quais se induziu hidropsia endolinfática experimental por obliteração do ducto e saco endolinfático na orelha direita durante 16 semanas, divididas em dois grupos: oito cobaias recebendo um inibidor da ONS II, a aminoguanidina, por via oral e um grupo de oito cobaias como controle. Comparamos as amplitudes das EOAPD nas médias geométricas de freqüências de 1062, 2187, 4375 e 7000Hz, os limiares eletrofisiológicos nas freqüências de 1000, 2000, 4000 e 6000Hz e a relação entre os potenciais de somação e de ação (PS/PA) entre os grupos. RESULTADOS: Não houve diferença significante nas EOAPD e na relação PS/PA entre os grupos. O grupo que recebeu a aminoguanidina apresentou menor elevação nos limiares eletrofisiológicos nas freqüências de 2000 (p&lt;0,05) e 6000 Hz (p&lt;0,05) na 12ª semana e nas freqüências de 1000 (p&lt;0,05), 2000 (p&lt;0,001), 4000 (p&lt;0,001) e 6000Hz (p&lt;0,001) na 16ª semana. CONCLUSÕES: O inibidor da ONS II reduziu a elevação dos limiares eletrofisiológicos na eletrococleografia na hidropsia endolinfática experimental.

Experimental endolymphatic hydrops under action of a type II nitric oxide synthase inhibitor: otoacoustic emissions evaluation and electrocochleography

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<0.05) And 6000 hz (p<0.05) In 12th postoperative week and at 1000 (p<0.05), 2000 (P<0.001), 4000 (P<0.001) And 6000 hz (p<0.001) At 16th postoperative week. Conclusions: nos ii inhibitor decreased the electrocochleography threshold elevation on experimental endolymphatic hydrops.

Diameter of the Cochlear Nerve in Endolymphatic Hydrops: Implications for the Etiology of Hearing Loss in Ménière's Disease

Endolymphatic hydrops (ELH) is an important histopathological hallmark of Ménière's disease. Experimental data from human temporal bones as well as animal models of the disorder have generally failed to determine the mechanism by which ELH or related pathology causes hearing loss. Hair cell and spiral ganglion cell counts in both human and animal case studies have not, for the most part, shown severe enough deterioration to explain associated severe sensorineural hearing loss. However a limited number of detailed ultrastructural studies have demonstrated significant reductions in dendritic innervation densities, raising the possibility that neurotoxicity plays an important role in the pathology of Ménière's disease (MD) as well as experimental endolymphatic hydrops (ELH). This study tests the hypothesis that neurotoxicity is an important primary mediator of injury to the hydropic ear and is reflected in measurable deterioration of the cochlear nerve in the animal model of ELH. This study also explores the previously presented hypothesis that cochlear injury in ELH is mediated through the actions of nitric oxide (NO) by evaluating whether hearing loss or various measures of cochlear damage can be ameliorated by administration of an agent that limits excess production of NO. Part one of the project involves the surgical induction of endolymphatic hydrops and correlation of long term hearing loss with histological parameters of ELH severity as well as cochlear nerve and eighth cranial nerve diameter measurements. In part two, aminoguanidine is administered orally to a separate set of hydropic animals in an attempt to limit cochlear injury presumably mediated by NO. Guinea pigs are subjected to surgical induction of unilateral endolymphatic hydrops after establishing baseline ABR thresholds at 2, 4, 8, 16, and 32 kHz. Threshold shifts are established prior to sacrifice at 4 to 6 months and temporal bones processed for light microscopy. Measurements of cochlear nerve and eighth cranial nerve maximal diameters as well as average maximal diameters are carried out and correlated to hearing loss and a semi-quantitative measure of hydrops severity. The identical experiments are carried out in animals treated with aminoguanidine, an inhibitor of inducible nitric oxide synthase. : The mean maximal diameter (n = 14) of the hydropic cochlear nerve was significantly reduced (432.14 +/- 43.18 vs. 479.28 +/- 49.22 microns, P = .0025) as compared to the control nerve. This was also seen in measures of the eighth cranial nerve (855.71 +/- 108.82 vs. 929 +/- 81.53 microns, P = 0.0003). Correlation studies failed to show correlation between hydrops severity and a cochlear nerve deterioration index (r = -0.0614, P = .8348). Similarly, hearing loss severity failed to correlate with cochlear nerve deterioration (r = 0.1300, P = .6577). There was a significant correlation between hearing loss and hydrops severity (r = 0.6148, P = .0193). Aminoguanidine treated animals (n = 5) also sustained nerve deterioration to the same degree as non-treated animals and there appeared to be no protective effect (at the dosage administered) against ELH related hearing loss, hydrops formation, or nerve deterioration. ELH results in significant deterioration of cochlear nerve and eighth cranial nerve maximal diameters in the guinea pig model. These findings are in accord with previous studies which detected ultrastructural evidence of dendritic damage and indicate that neural injury is of sufficient severity to result in light microscopic evidence of cochlear nerve and eighth cranial nerve deterioration. These data support the concept that the principle pathological insult in ELH is a form of neurotoxicity, especially in light of previous studies which indicate relative preservation of hair cells at similar points in time. The lack of correlation between the severity of hydrops and nerve deterioration suggests that nerve deterioration is independent of hydrops severity.

Letter to the Editor

In order to find out whether it is possible to visualize experimental endolymphatic hydrops in the cochlea with magnetic resonance imaging (MRI) at 4.7 T, we used 11 guinea pigs. Five normal guinea pigs were used as controls. Early manifestation of endolymphatic hydrops was evaluated in endolymphatic sac (ES)-intact animals (n = 6), and advanced manifestation in ES-damaged animals (n = 5) by means of MRI with gadolinium-diethylenetriaminepentaacetate-bismethylamide (Gd-DTPA-BMA) contrast agent. Hearing was tested with electrocochleography. The surface area of 3 partitions of the cochlea was used to quantify endolymphatic hydrops. The fine structure of the 3 partitions of the cochlea was visualized with MRI in all animals, as Gd-DTPA-BMA appeared mainly in the scala tympani and scala vestibuli. As early as 5 days after endolymphatic sac surgery, endolymphatic hydrops started to appear as visualized by MRI and also verified with histology. Severe damage to the inner ear barrier with Gd-DTPA-BMA leakage into the scala media was detected with MRI in 1 ES-damaged animal that had a 60-dB hearing loss. To conclude, endolymphatic hydrops can be visualized with high-resolution MRI by means of Gd-DTPA-BMA, and it is possible to quantify the extent of endolymphatic hydrops. Damage to the inner ear barrier or possible rupture of membranes can be shown with the assistance of Gd-DTPA-BMA.

Effects of hyperbaric therapy on function and morphology of Guinea pig cochlea with endolymphatic hydrops.

The objective of this study was to investigate the effect on experimental endolymphatic hydrops in guinea pigs after hyperbaric therapy. The histopathologic character of Ménière's disease is the presence of endolymphatic hydrops. Endolymphatic hypertension could be one of the factors resulting from endolymphatic hydrops. Some treatments of Ménière's disease are aimed toward preventing the endolymphatic hypertension. Exposure to pressure change has risen in recent years. Thirty-two guinea pigs were operated on the right ears to induce endolymphatic hydrops by obliterating the endolymphatic sac through an extradural posterior cranial fossa approach. After 5 weeks' survival, 12 guinea pigs were put into a chamber with an absolute atmospheric pressure of 2.2 for 3 weeks (90 minutes once a day 5 times a week). We observed the morphologic and functional changes in guinea pig cochleae of the pressure group, 4-week hydrops group (n = 10), 8-week hydrops group (n = 10), and the normal group (n = 10). We measured the hearing threshold of the auditory brainstem response, the 70-dB SPL action potential (AP) latency, the ratio of 70-dB SPL summating potential magnitude to action potential magnitude (-SP/AP) of the electrocochleogram, and the maximum scala media area (SMA) ratio, respectively. The average 70-dB SPL-SP/AP magnitude of right ears (0.29 +/- 0.09) and the average maximum SMA ratio (2.23 +/- 0.20) in the pressure group were significantly less than that in the 8-week hydrops group (0.69 +/- 0.15 and 4.04 +/- 0.52, respectively) with the same survival time (p < 0.05). The results in the pressure group were almost as similar as that in the 4-week hydrops group (0.29 +/- 0.13 and 2.22 +/- 0.20, respectively) (p > 0.05). The average hearing threshold of ABR of right ears in the pressure group (36.67 +/- 14.30-dB SPL) was lower than that of the 8-week hydrops group (44 +/-1 4.30-dB SPL), but the difference was insignificant (p > 0.05). The average 70-dB SPL AP latency of right ears in the pressure group was not significantly different from those of the 8-week hydrops group, the 4-week hydrops group, or the normal group (p > 0.05). Our findings suggest hyperbaric therapy can significantly suppress the development of endolymphatic hydrops and improve cochlear function in guinea pigs. This study provided strong evidence for the development of pressure treatment of Ménière's disease without destroying the inner ear.

In vivo visualization of endolymphatic hydrops in guinea pigs: magnetic resonance imaging evaluation at 4.7 tesla.

In order to find out whether it is possible to visualize experimental endolymphatic hydrops in the cochlea with magnetic resonance imaging (MRI) at 4.7 T, we used 11 guinea pigs. Five normal guinea pigs were used as controls. Early manifestation of endolymphatic hydrops was evaluated in endolymphatic sac (ES)-intact animals (n = 6), and advanced manifestation in ES-damaged animals (n = 5) by means of MRI with gadolinium-diethylenetriaminepentaacetate-bismethylamide (Gd-DTPA-BMA) contrast agent. Hearing was tested with electrocochleography. The surface area of 3 partitions of the cochlea was used to quantify endolymphatic hydrops. The fine structure of the 3 partitions of the cochlea was visualized with MRI in all animals, as Gd-DTPA-BMA appeared mainly in the scala tympani and scala vestibuli. As early as 5 days after endolymphatic sac surgery, endolymphatic hydrops started to appear as visualized by MRI and also verified with histology. Severe damage to the inner ear barrier with Gd-DTPA-BMA leakage into the scala media was detected with MRI in 1 ES-damaged animal that had a 60-dB hearing loss. To conclude, endolymphatic hydrops can be visualized with high-resolution MRI by means of Gd-DTPA-BMA, and it is possible to quantify the extent of endolymphatic hydrops. Damage to the inner ear barrier or possible rupture of membranes can be shown with the assistance of Gd-DTPA-BMA.

Different regulation of connexin26 and ZO-1 in cochleas of developing rats and of guinea pigs with endolymphatic hydrops.

Using confocal microscopy and morphometry, we analyzed the expression of connexin26 (Cx26) and ZO-1 in rat cochlea during the postnatal period to elucidate spatiotemporal changes in gap junctions and tight junctions during auditory development. We also studied changes in these junctions in experimental endolymphatic hydrops in the guinea pig. In the adult rat cochlear lateral wall, Cx26 was detected in fibrocytes in the spiral ligament and in the basal cell layer of the stria vascularis, whereas ZO-1 was detected in the apical surfaces of marginal cells and in the basal cell layer. During postnatal development, Cx26 expression increased mainly in the spiral ligament, whereas ZO-1 expression increased in the basal cell layer. The morphometry of Cx26 showed a sigmoid time course with a rapid increase on postnatal day (PND) 14, whereas that of ZO-1 showed a marked increase on PND 7. In experimental endolymphatic hydrops, the expression of Cx26 significantly decreased, whereas there were no obvious changes in the expression of ZO-1. These results indicate that gap junctions and tight junctions in the cochlea increase in a different spatiotemporal manner during the development of auditory function and that gap junctions and tight junctions in the cochlea are differentially regulated in experimental endolymphatic hydrops. (J Histochem Cytochem 49:573-586, 2001)

Chronological changes in the eight nerve compound action potential in experimental endolymphatic hydrops

Chronological changes in the eight nerve compound action potential in experimental endolymphatic hydrops

Studies of Cochlear Blood Flow in Guinea Pigs with Endolymphatic Hydrops

Laser Doppler flowmetry was used to assess cochlear blood flow (CoBF) in guinea pigs with experimental endolymphatic hydrops following intravenous infusion of 5 types of drugs: 50% glycerol, 70% isosorbide, 20% mannitol, 7% sodium bicarbonate, and 1% diphenidol. The magnitude of the CoBF changes following infusion tended to be smaller in the hydropic ears than in the normal control ears. A significant reduction in CoBF changes was observed in hydropic ears infused with isosorbide and sodium bicarbonate. These results suggest that the cochlear microvascular sensitivity to various stimuli such as drug infusion is reduced in hydropic ears. This may result from atrophy of the stria vascularis which is often observed in the hydropic ears of guinea pigs. Thus it seems likely that the same reaction occurs in the inner ear of patients with Ménière’s disease in whom atrophy of the stria vascularis is also presumed to exist in conjunction with extensive endolymphatic hydrops. Therefore, it seems probable that the function of the microvasculature of the stria vascularis is impaired in the inner ear of patients with Ménière’s disease, resulting in the slow progressive deterioration of the inner ear with time.

Failure of Forskolin to Elevate the Endocochlear Potential in Experimental Endolymphatic Hydrops of the Guinea Pig

The effect of forskolin (FSK) on the endocochlear potential (EP) in scala media (SM) was examined in experimental endolymphatic hydrops of the guinea pig. Two weeks after obliteration of the endolymphatic sac the EP of hydroptic ears and that of the contralateral control ears were measured by means of microelectrodes. The perfusion of scala vestibuli (SV) with FSK (200 w M) produced EP elevation in the contralateral control ears but failed to do so in the experimental hydroptic ears. Histological examination of experimental endolymphatic hydrops showed mild hydrops with intact appearance of outer and inner hair cells, and the stria vascularis. The mechanism underlying the failure of FSK to elevate the EP in experimental endolymphatic hydrops is discussed.

Laboratory Experience With Experimental Endolymphatic Hydrops

Experimental endolymphatic hydrops refers to the creation of hydrops in the experimental animal and represents a histologic correlate for Meniere's disease. Details of the surgical means to create this condition in guinea pigs are provided. Alterations in endolymph fluid composition and relative endolymph pressure occur with hydrops. Deterioration in auditory and vestibular function secondary to hydrops can develop.