The Severity of Infection Determines the Localization of Damage and Extent of Sensorineural Hearing Loss in Experimental Pneumococcal Meningitis.

Perny, Michael; Roccio, Marta; Grandgirard, Denis; Solyga, Magdalena; Senn, Pascal; Leib, Stephen (2016). The Severity of Infection Determines the Localization of Damage and Extent of Sensorineural Hearing Loss in Experimental Pneumococcal Meningitis. Journal of neuroscience, 36(29), pp. 7740-7749. Society for Neuroscience 10.1523/JNEUROSCI.0554-16.2016

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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. SIGNIFICANCE STATEMENT Hearing loss is a neurofunctional deficit occurring in up to 30% of patients surviving pneumococcal meningitis (PM). Here, we analyze the correlation between the severity of infection and the inflammatory response in the CSF, the tonotopic distribution of neurosensory pathologies in the cochlea, and the long-term hearing function in a rat model of pneumococcal meningitis. Our study identifies the severity of infection as the key determinant of long-term hearing loss, underlining the importance of the prompt institution of antibiotic therapy in patients suffering from PM. Furthermore, our findings reveal in detail the spatial loss of cochlear neurosensory cells, providing new insights into the pathogenesis of meningitis-associated hearing loss that reveal new starting points for the development of otoprotective therapies.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ear, Nose and Throat Disorders (ENT)
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Perny, Michael; Roccio, Marta; Grandgirard, Denis; Senn, Pascal and Leib, Stephen

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0270-6474

Publisher:

Society for Neuroscience

Funders:

[UNSPECIFIED] European Commission (OTOSTEM Grant FP7-Health-603029, to P.S., S.L.L.)
[4] Swiss National Science Foundation

Language:

English

Submitter:

Stephen Leib

Date Deposited:

06 Jan 2017 14:13

Last Modified:

13 Feb 2017 08:38

Publisher DOI:

10.1523/JNEUROSCI.0554-16.2016

PubMed ID:

27445150

Additional Information:

Senn and Leib contributed equally to this work

Uncontrolled Keywords:

animal model; hair cells; pneumococcal meningitis; sensorineural hearing loss; spiral ganglion neurons; streptococcus pneumonia

BORIS DOI:

10.7892/boris.90873

URI:

https://boris.unibe.ch/id/eprint/90873

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