Evaluation of the mouse model for acute otitis media
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Carol J MacArthur1, Steven H Hefeneider, J Beth Kempton
1Department of Otolaryngology and Oregon Hearing Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, PV-01, Portland, OR 97239-3098, USA. macarthc@ohsu.edu
Abstract:
Various animal models have been employed for otitis media research. The mouse has been studied less, in spite of its many advantages. To better understand the suitability of the mouse for studies of otitis media, an evaluation was made of its middle ear inflammatory processes following inoculation with heat-killed Streptococcus pneumoniae (strain 6A), one of the three most common bacteria to cause otitis media in the human. A total of 94 BALB/c mice were injected transtympanically with three concentrations of heat-killed bacteria (10(4), 10(6), and 10(9) organisms per ml) and inflammation evaluated with both histologic examination and auditory brainstem response audiometry. Dose-related measures of the time course of inflammation showed it was maximal at 3 days. PBS-injected control mice also demonstrated some degree of middle ear inflammation. Therefore, inflammation measures from PBS injected mice were used as the threshold above which histologic inflammatory changes would be considered a response to bacteria. These quantitative comparisons of bacterial and PBS inoculations revealed the most significant middle ear measures of inflammation were amount of fluid in the middle ear, tympanic membrane thickness, and number of inflammatory cells. The induction of middle ear inflammation in the mouse demonstrated the applicability of this model for investigations of otitis media.
Insights
The mouse middle ear effectively models otitis media inflammation using heat-killed Streptococcus pneumoniae. This model, evaluated via histology and auditory testing, shows inflammation peaking at 3 days, validating its use in otitis media research.
Area of Science:
- Otolaryngology
- Microbiology
- Immunology
Background:
- Otitis media is a common childhood infection often caused by Streptococcus pneumoniae.
- Animal models are crucial for studying otitis media pathogenesis and treatment.
- The mouse model for otitis media has been less explored despite its advantages.
Purpose of the Study:
- To evaluate the suitability of the BALB/c mouse as an animal model for otitis media research.
- To characterize middle ear inflammatory responses to heat-killed Streptococcus pneumoniae.
- To establish quantitative measures of inflammation in the mouse middle ear.
Main Methods:
- Transtympanic inoculation of 94 BALB/c mice with heat-killed Streptococcus pneumoniae at varying concentrations (10^4, 10^6, 10^9 organisms/ml).
- Histologic examination and auditory brainstem response audiometry to assess middle ear inflammation.
- Comparison with phosphate-buffered saline (PBS)-injected controls to establish inflammatory thresholds.
Main Results:
- Middle ear inflammation in mice peaked at 3 days post-inoculation in a dose-dependent manner.
- Key indicators of inflammation included middle ear fluid accumulation, tympanic membrane thickening, and inflammatory cell infiltration.
- Histologic changes above PBS-injected control thresholds were considered significant bacterial responses.
Conclusions:
- The mouse model is suitable for investigating otitis media due to reproducible inflammatory responses.
- This model allows for quantitative assessment of key otitis media inflammatory markers.
- Further research utilizing this mouse model can advance understanding and treatment of otitis media.
