Hair Cell Regeneration And Innervation In The Mouse Vestibule Traumatized By Streptomycin

Objective:To evaluate the hair cell regeneration in the mouse vestibule traumatized by two different doses of streptomycin.Methods:Two different doses of streptomycin were infused into mouse left posterior semicircular canal, leading to moderate and severe lesions in the mouse vestibular epithelium, respectively. Using immunofluorescence staining, scanning electron microscope and plastic section, we assessed morphological features and hair cell regeneration in the mouse utricle at different time point after streptomycin treatment.Results:In the moderately traumatized mouse utricular epithelium, numerous hair cells were lost but supporting cells survived. New hair cells, characterized by immature hair bundles, were found within 2 week after the insult, and the numbers increased as time advanced. However, the morphology of new hair cells was different from that of normal ones and the number was limited as well. In contrast, both hair cells and supporting cells were damaged in the severely traumatized mouse utricle, resulting in a monolayer of very thin flat cells, which was defined as flat epithelium. The capacity for spontaneous hair cell regeneration in the flat epithelium was dramaticly diminished, and some flat cells were neither hair cells nor supporting cells.Conclusion:Our data suggest that mouse vestibular sensory epithelium has a capacity for spontaneous hair cell regeneration after damage by streptomycin. A severe lesion dramaticly diminishes the capacity, leading to a flat epithelium.Objective:To investigate the process of spontaneous regeneration in the mouse vestibular epithelium vis-a-vis changes in Notch signaling and Atohl expression.Methods:We induced a moderate lesion in the mouse vestibular epithelium by infusing streptomycin into the posterior semicircular canal, and examined Notch signaling molecules and their mRNA expression levels in the mouse utricle by immunofluorescence staining and quantitative real-time polymerase chain reaction, respectively.Results:Immunohistochemistry data showed that Jagged1 was expressed in the supporting cells of the normal utricle and remained in these cells after the lesion. Atohl immuno-fluorescence, undetectable in the normal mature mouse utricle, appeared after trauma in nuclei with or without myosinâ…¦a labeling. Using quantitative real-time polymerase chain reaction, we detected down-regulation of Hes5, up-regulation of Atohl and no changes in levels of Notch 1, Jagged 1 and Hes1.Conclusion:Our results suggest that the response of cells in the utricle to an ototoxic trauma involve changes of Notch signaling molecules and Atohl expression. The spontaneous hair cell regeneration may arise earlier than previously thought and Atohl up-regulation may be initiated by more than one signaling pathway. Objective:To study changes of synapses, nerve fibers and vestibular ganglion neurons in the mouse vestibule traumatized by two different doses of streptomycin.Methods:We induced moderate or severe lesions in the mouse vestibular epithelium by infusion of two different doses of streptomycin into mouse posterior semicircular canal. The Neurofilament 200 antibody was used to label synapses and nerve fibers in the utricular sensory epithelium at different time point after streptomycin treatment. The density of survival of superior vestibular ganglion neurons was qualified in plastic sections of superior vestibular ganglion neurons.Results:At 1 month following the moderate or severe lesion, nerve calyces were almost all gone. However, nerve fibers survived and superior vestibular ganglion neurons showed no changes in either morphology or density. At 3 months after the severe lesion, the sensory epithelium was still devoid of nerve calyces. The density of superior ganglion neurons was decreased significantly.Conclusion:Nerve fibers survive for a while in the severely traumatized mouse vestibular sensory epithelium. Therefore, potential treatment to restore balance by stem cell or vestibular prosthesis implantation may benefit from the persistence of surviving neurons.