Format

Send to

Choose Destination
J Neurosci. 2016 Jul 20;36(29):7740-9. doi: 10.1523/JNEUROSCI.0554-16.2016.

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

Author information

1
Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, 3001 Bern, Switzerland, Laboratory of Inner Ear Research, Department of Clinical Research, University of Bern and University Department of Otorhinolaryngology, Head & Neck Surgery, Inselspital, 3008 Bern, Switzerland, Cluster for Regenerative Neuroscience, Department of Clinical Research, University of Bern, 3008 Bern, Switzerland.
2
Laboratory of Inner Ear Research, Department of Clinical Research, University of Bern and University Department of Otorhinolaryngology, Head & Neck Surgery, Inselspital, 3008 Bern, Switzerland, Cluster for Regenerative Neuroscience, Department of Clinical Research, University of Bern, 3008 Bern, Switzerland.
3
Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, 3001 Bern, Switzerland, Cluster for Regenerative Neuroscience, Department of Clinical Research, University of Bern, 3008 Bern, Switzerland.
4
Laboratory of Inner Ear Research, Department of Clinical Research, University of Bern and University Department of Otorhinolaryngology, Head & Neck Surgery, Inselspital, 3008 Bern, Switzerland, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Geneva, 1205 Geneva, Switzerland, and Cluster for Regenerative Neuroscience, Department of Clinical Research, University of Bern, 3008 Bern, Switzerland.
5
Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, 3001 Bern, Switzerland, Cluster for Regenerative Neuroscience, Department of Clinical Research, University of Bern, 3008 Bern, Switzerland stephen.leib@ifik.unibe.ch.

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.

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.

KEYWORDS:

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

PMID:
27445150
DOI:
10.1523/JNEUROSCI.0554-16.2016
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center