期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 29, 页码 7740-7749出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0554-16.2016
关键词
animal model; hair cells; pneumococcal meningitis; sensorineural hearing loss; spiral ganglion neurons; streptococcus pneumonia
资金
- European Commission [FP7-Health-603029]
- Swiss National Science Foundation [310030_162583]
- Microscopy Imaging Center of the University of Bern
- Swiss National Science Foundation (SNF) [310030_162583] Funding Source: Swiss National Science Foundation (SNF)
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-1 beta, interleukin-6, tumor necrosis factor alpha, interleukin-10, and interferon-gamma 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.
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