51 research outputs found
Characterization of a pneumococcal meningitis mouse model
<p>Abstract</p> <p>Background</p> <p><it>S. pneumoniae </it>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.</p> <p>Methods</p> <p>Adult mice (C57BL/6) were inoculated in the cisterna magna with increasing doses of <it>S. pneumoniae </it>serotype 3 colony forming units (CFU; n = 24, 10<sup>4</sup>, 10<sup>5</sup>, 10<sup>6 </sup>and 10<sup>7 </sup>CFU) and survival studies were performed. Cerebrospinal fluid (CSF), brain, blood, spleen, and lungs were collected. Subsequently, mice were inoculated with 10<sup>4 </sup>CFU <it>S. pneumoniae </it>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<sup>®</sup>) in CSF, blood and brain. Meningeal inflammation, neutrophil infiltration, parenchymal and subarachnoidal hemorrhages, microglial activation and hippocampal apoptosis were assessed in histopathological studies.</p> <p>Results</p> <p>Lower doses of bacteria delayed onset of illness and time of death (median survival CFU 10<sup>4</sup>, 56 hrs; 10<sup>5</sup>, 38 hrs, 10<sup>6</sup>, 28 hrs. 10<sup>7</sup>, 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 10<sup>4 </sup>CFU of <it>S. pneumoniae</it>, 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.</p> <p>Conclusion</p> <p>We have developed and validated a murine model of pneumococcal meningitis.</p
Increased lung inflammation with oxygen supplementation in tracheotomized spontaneously breathing rabbits: an experimental prospective randomized study
Lethal control of an apex predator has unintended cascading effects on forest mammal assemblages
An atypical case of choroidal neovascularization associated with pseudoxanthoma elasticum treated with intravitreal bevacizumab: a case report
Culinary practices: preparation techniques and consumption of Basotho cereal breads in Lesotho
Identification and Characterization of a δ-Cadinol Synthase Potentially Involved in the Formation of Boreovibrins in Boreostereum vibrans of Basidiomycota
Cattle culture and colour symbolism as reflected in selected artworks of Sotho-Tswana in South Africa
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