Characterization of a pneumococcal meningitis mouse model

BMC Infectious Diseases

Diederik van de Beek²  Tom van der Poll³  Dirk Troost⁴  Madelijn Geldhoff¹  Barry Mook-Kanamori¹ 

[1]Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, the Netherlands

[2]Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, P.O. Box 22660, Amsterdam 1100DD, The Netherlands

[3]Center for Experimental and Molecular Medicine (CEMM), Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, the Netherlands

[4]Department of (Neuro) Pathology, Academic Medical Center, Amsterdam, the Netherlands

关键词: Infectious diseases;    Animal model;    Neurology;    Critical care;    Meningitis;   

Others  :  1175419
DOI  :  10.1186/1471-2334-12-71

 received in 2011-12-19, accepted in 2012-03-28,  发布年份 2012

【 摘 要 】

Background

S. pneumoniae is the most common causative agent of meningitis, and is associated with high morbidity and mortality. We aimed to develop an integrated and representative pneumococcal meningitis mouse model resembling the human situation.

Methods

Adult mice (C57BL/6) were inoculated in the cisterna magna with increasing doses of S. pneumoniae serotype 3 colony forming units (CFU; n = 24, 10⁴, 10⁵, 10⁶ and 10⁷ CFU) and survival studies were performed. Cerebrospinal fluid (CSF), brain, blood, spleen, and lungs were collected. Subsequently, mice were inoculated with 10⁴ CFU S. pneumoniae serotype 3 and sacrificed at 6 (n = 6) and 30 hours (n = 6). Outcome parameters were bacterial outgrowth, clinical score, and cytokine and chemokine levels (using Luminex^®) in CSF, blood and brain. Meningeal inflammation, neutrophil infiltration, parenchymal and subarachnoidal hemorrhages, microglial activation and hippocampal apoptosis were assessed in histopathological studies.

Results

Lower doses of bacteria delayed onset of illness and time of death (median survival CFU 10⁴, 56 hrs; 10⁵, 38 hrs, 10⁶, 28 hrs. 10⁷, 24 hrs). Bacterial titers in brain and CSF were similar in all mice at the end-stage of disease independent of inoculation dose, though bacterial outgrowth in the systemic compartment was less at lower inoculation doses. At 30 hours after inoculation with 10⁴ CFU of S. pneumoniae, blood levels of KC, IL6, MIP-2 and IFN- γ were elevated, as were brain homogenate levels of KC, MIP-2, IL-6, IL-1β and RANTES. Brain histology uniformly showed meningeal inflammation at 6 hours, and, neutrophil infiltration, microglial activation, and hippocampal apoptosis at 30 hours. Parenchymal and subarachnoidal and cortical hemorrhages were seen in 5 of 6 and 3 of 6 mice at 6 and 30 hours, respectively.

Conclusion

We have developed and validated a murine model of pneumococcal meningitis.

【 授权许可】

   
2012 Mook-Kanamori et al; licensee BioMed Central Ltd.

【 图 表 】

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