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Title

The severity of infection determines the localization of damage and extent of sensorineural hearing loss in experimental pneumococcal meningitis

Authors
Perny, Michael
Roccio, Marta
Grandgirard, Denis
Solyga, Magdalena
Leib, Stephen L
Published in Journal of Neuroscience. 2016, vol. 36, no. 29, p. 7740-7749
Abstract Hearing loss is an important sequela of pneumococcal meningitis (PM), occurring in up to 30% of survivors. The role of the severity of infection on hearing function and pathomorphological consequences in the cochlea secondary to PM have not been investigated to date. Using a well-established model of PM, we systematically investigated the functional hearing outcome and the long-term fate of neurosensory cells in the cochlea, i.e., hair cells and spiral ganglion neurons (SGNs), with a focus on their tonotopic distribution. Intracisternal infection of infant rats with increasing inocula of Streptococcus pneumoniae resulted in a dose-dependent increase in CSF levels of interleukin-1β, interleukin-6, tumor necrosis factor α, interleukin-10, and interferon-γ in acute disease. The severity of long-term hearing loss at 3 weeks after infection, measured by auditory brainstem response recordings, correlated to the initial inoculum dose and to the levels of proinflammatory cytokines determined in the acute phase of PM. Quantitative cochlear histomorphology revealed a significant loss of SGNs and outer hair cells that strongly correlated to the level of infection, with the most severe damage occurring in the basal part of the cochlea. Inner hair cells (IHCs) were not significantly affected throughout the entire cochlea. However, surviving IHCs lost synaptic connectivity to remaining SGNs in all cochlear regions. These findings provide evidence that the inoculum concentration, i.e., severity of infection, is the major determinant of long-term morphological cell pathologies in the cochlea and functional hearing loss.
Keywords Animal modelHair cellsPneumococcal meningitisSensorineural hearing lossSpiral ganglion neuronsStreptococcus pneumonia
Identifiers
PMID: 27445150
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Structures
Research group Groupe Pascal Senn (954)
Projects FNS: 310030_162583
FP7: OTOSTEM
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PERNY, Michael et al. The severity of infection determines the localization of damage and extent of sensorineural hearing loss in experimental pneumococcal meningitis. In: Journal of Neuroscience, 2016, vol. 36, n° 29, p. 7740-7749. https://archive-ouverte.unige.ch/unige:121871

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Deposited on : 2019-08-26

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