Endolymphatic hydrops induced by different mechanisms responds differentially to spironolactone: a rationale for understanding the diversity of treatment responses in hydropic inner ear disease

Degerman, Eva; Zandt, René in ‘t; Pålbrink, Ann-Ki; Magnusson, Måns

doi:10.1080/00016489.2019.1616819

Cited by 11 publications

(10 citation statements)

References 20 publications

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“…The dose of desmopressin reported to induce EH models was variable, but there was evidence supporting increasing dosage and injection days can provide a more severe EH status in animal models at a low dose level ( Takeda et al, 2000 ; Katagiri et al, 2014 ). The dose of 4–6 μg/kg weight has been widely used for EH guinea pigs modeling ( Degerman et al, 2019 ; Jiang et al, 2019 ). Considering the potential for long-time medication tolerance, we increased the dose of desmopressin for our animal models ( Takeda et al, 2000 ).…”

Section: Methodsmentioning

confidence: 99%

The Effect of Endolymphatic Hydrops and Mannitol Dehydration Treatment on Guinea Pigs

Wang

et al. 2022

Front. Cell. Neurosci.

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BackgroundEndolymphatic hydrops (EH) is considered as the pathological correlate of Menière’s disease (MD) and cause of hearing loss. The mechanism of EH, remaining unrevealed, poses challenges for formalized clinical trials.ObjectiveThis study aims to investigate the development of hearing loss, as well as the effect of dehydration treatment on EH animal models.MethodsIn this study, different severity EH animal models were created. The laser Doppler vibrometer (LDV) and auditory brainstem responses (ABR) were used to study the effects of EH and the dehydration effects of mannitol. The LDV was used to measure the vibration of the round window membrane (RWM) reflecting the changes in inner ear impedance. ABR was used to evaluate the hearing changes. Furthermore, tissue section and scanning electron microscopy (SEM) observations were used to analyze the anatomical change to the cochlea and outer hair cells.ResultsThe RWM vibrations decreased with the severity of EH, indicating an increase in the cochlear impedance. The dehydration therapy lowered the impedance to restore acoustic transduction in EH 10- and 20-day animal models. Simultaneously, the ABR thresholds increased in EH models and were restored after dehydration. Moreover, a difference in the hearing was found between ABR and LDV results in severe EH animal models, and the dehydration therapy was less effective, indicating a sensorineural hearing loss (SNHL).ConclusionEndolymphatic hydrops causes hearing loss by increasing the cochlear impedance in all tested groups, and mannitol dehydration is an effective therapy to restore hearing. However, SNHL occurs for the EH 30-day animal models, limiting the effectiveness of dehydration. Our results suggest the use of dehydrating agents in the early stage of EH.

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Section: Methodsmentioning

confidence: 99%

The Effect of Endolymphatic Hydrops and Mannitol Dehydration Treatment on Guinea Pigs

Wang

et al. 2022

Front. Cell. Neurosci.

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“…In an experimental study, Degerman et al showed that spironolactone blocks the phosphodiesterase 4 (PDE4) pathway, involved in the generation of endolymphatic hydrops [ 222 ].…”

Section: Methodsmentioning

confidence: 99%

Drug–Drug Interactions in Vestibular Diseases, Clinical Problems, and Medico-Legal Implications

Mizio

Marcianò

Palleria

et al. 2021

IJERPH

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Peripheral vestibular disease can be treated with several approaches (e.g., maneuvers, surgery, or medical approach). Comorbidity is common in elderly patients, so polytherapy is used, but it can generate the development of drug–drug interactions (DDIs) that play a role in both adverse drug reactions and reduced adherence. For this reason, they need a complex kind of approach, considering all their individual characteristics. Physicians must be able to prescribe and deprescribe drugs based on a solid knowledge of pharmacokinetics, pharmacodynamics, and clinical indications. Moreover, full information is required to reach a real therapeutic alliance, to improve the safety of care and reduce possible malpractice claims related to drug–drug interactions. In this review, using PubMed, Embase, and Cochrane library, we searched articles published until 30 August 2021, and described both pharmacokinetic and pharmacodynamic DDIs in patients with vestibular disorders, focusing the interest on their clinical implications and on risk management strategies.

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“…Imaging technology, including MRI, might be developed as a critical tool for evaluating ELH in animal models for MD. In a recent study, ELH in mice was assessed using a high resolution 9.4 T field strength MRI [41]. Furthermore, light sheet fluorescence microscopy (LSFM) can be used as a means to obtain highly resolved 3D visualization of endolymphatic fluid movements; this has enabled researchers to examine the entire inner ear of experimental animals, en bloc, with subcellular resolution.…”

Section: Confirmation Methods In Animal Models Of Endolymphatic Hydropsmentioning

confidence: 99%

“…We introduced fluorescein isothiocyanate dextran (FITC-dex) and artificial endolymph into the scala media of anesthetized guinea pigs via a glass micropipette (Fig. 2) [41]. When more than 2.5 mL of FITC-dex was injected into the scala media, FITC-dex was observed in the SSCs, utricle, and endolymphatic duct.…”

Section: Confirmation Methods In Animal Models Of Endolymphatic Hydropsmentioning

confidence: 99%

Experimental Animal Models for Meniere’s Disease: A Mini-Review

Seo

Brown

2020

J Audiol Otol

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Several novel animal models that represent the pathophysiological process of endolymphatic hydrops (ELH) of Meniere’s disease (MD) have been developed. Animal models are important to identify and characterize the pathophysiology of ELH and to corroborate molecular and genetic findings in humans. This review of the current animal models will be useful in understanding the pathophysiology of and developing proper treatments for MD. Surgical animal models will be replaced by medication-induced animal models. Study models previously developed in guinea pigs will be developed in several smaller animals for ease of conducting molecular analysis. In this review, we provided updated resources including our previous studies regarding the current and desirable animal models for MD.

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Endolymphatic hydrops induced by different mechanisms responds differentially to spironolactone: a rationale for understanding the diversity of treatment responses in hydropic inner ear disease

Abstract: Endolymphatic hydrops induced by different mechanisms responds differentially to spironolactone: a rationale for understanding the diversity of treatment responses in hydropic inner ear disease ,

Cited by 11 publications

References 20 publications

The Effect of Endolymphatic Hydrops and Mannitol Dehydration Treatment on Guinea Pigs

The Effect of Endolymphatic Hydrops and Mannitol Dehydration Treatment on Guinea Pigs

Drug–Drug Interactions in Vestibular Diseases, Clinical Problems, and Medico-Legal Implications

Experimental Animal Models for Meniere’s Disease: A Mini-Review

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