Characteristics Of Vestibular Impairment In Meniere's Disease And Cellular Remodeling In The Medial Vestibular Nuclei Induced By Unilateral Labyrinthectomy

Background: Vestibular damage can result in dysfunction of the vestibular neural circuit.Give the complex anatomy and the limited examination technique,the imaging and pathological characteristics of the vestibular disorder remains unclear,and the acute vestibular compensation mechanism is still enigmatic.Objective: This study aimed to explore the features of EH and its glycerol-induced dynamics and pathological alterations in the central portion of the vestibular nerve(VN)in Menière's disease(MD),and to identify cell composition and cell-type-specific transcriptional features in MVN which is essential for understanding its functions in early vestibular compensation.Methods: Intratympanic gadolinium-enhanced MRI combined with glycerol test was performed in the MD affected ears.The borders of endolymphatic and total lymphatic space were contoured on the axial MRI slices to evaluate the volume of hydrops in both the cochlear and vestibular regions.Segments of VN from patients underwent vestibular neurectomy were carefully removed for histopathological examination.In a mouse model of unilateral labyrinthectomy,spontaneous action potentials of bilateral nucleus neurons were recorded by patch clamp in brain slices containing MVN.Immunofluorescence was used to detect the activation of reactive astrocytes.12,370 cells in MVN were analyzed by single-cell sequencing to identify the cell types and gene expression features.Results: After glycerol ingestion,vestibular EH decreased in all patients,whereas cochlear EH significantly decreased only in patients with positive glycerol test results.Moreover,the dehydrating role of glycerol was positively correlated with the baseline cochlear hydrops level.Histopathological examination revealed evidence of various types of chronic VN impairment,including the formation of corpora amylacea(CA),axon atrophy,and severe damage to the myelin sheath.Electron microscopy revealed membranous whorls within dilated Schmidt–Lanterman incisures,the formation of myeloid bodies,dysmyelination,and demyelination.Unexpectedly,we observed a positive correlation between the density of CA in VN tissue and the duration of disease,as well as the degree of hearing impairment,independent of age.The frequency of spontaneous firing rate of neurons increased in ipsilateral MVN.GFAP expression in reactive astrocytes is upregulated in ipsilateral MVN.Eight types of cells were identified in MVN,among which neurons,astrocytes,and oligodendrocytes exhibited differential transcriptional features between the bilateral side after unilateral labyrinthectomy.Conclusion:MRI provides evidence that glycerol administration improves hearing threshold via dehydrating the EH.In the cochlear region,the baseline level of cochlear EH is a closely related factor for the validity of the glycerol test,whereas EH is consistently dehydrated in the vestibular component.Deformation of subcellular organelles in the central portion of the VN is one of the key pathological indicators for the progressive severity and intractability of vertigo and support a vestibular nerve degeneration.Cell-remodeling of MVN involved in the acute vestibular compensation induced by unilateral labyrinthectomy.This work provided a comprehensive transcriptional perspective of MVN in early vestibular compensation at the single-cell resolution.