کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
921986 | 1473927 | 2014 | 17 صفحه PDF | دانلود رایگان |
Interferon-gamma is known to play a complex modulatory role in immune defence during microbial infections. Its actions in pneumococcal meningitis, however, remain ill-defined. Here, a pathological role for IFN-γ was demonstrated using a murine model of pneumococcal meningitis, in that C57BL/6J mice deficient in this pro-inflammatory cytokine (IFN-γ−/−) showed less severe acute and long-term neuropathology following intracerebral challenge with Streptococcus pneumoniae. The absence of IFN-γ significantly lengthened the survival of mice that otherwise would have developed fatal clinical signs within two days of CNS infection. Compared to their wild-type counterparts, IFN-γ−/− mice showed a diminished inflammatory response (attenuated levels of pro-inflammatory cytokines in the cerebrospinal fluid) and milder brain pathologies (less BBB permeability to protein and brain haemorrhage) during the acute phase of disease. Following a full regime of antibiotic treatment, we found substantial brain injuries in the wild-type mice 10 days after infection. IFN-γ−/− mice, however, showed decreased neuronal damage in both hippocampus and cortex. In the longer term (≈10 weeks p.i.), the wild-type mice that had survived meningitis due to antibiotic treatment had neurobehavioural abnormalities including diurnal hypoactivity, nocturnal hyperactivity and impaired performance in a discrimination reversal task. IFN-γ−/− mice, concomitantly tested in the automated IntelliCage platform, had reduced behavioural and cognitive disorders compared to wild-type mice. Both IFN-γ−/− and wild-type survivors of pneumococcal meningitis showed impaired working memory in the IntelliCage-based complex patrolling task. These observations indicate an association between IFN-γ-driven acute brain pathology and the long-term neurological sequelae resulting from pneumococcal meningitis.
Journal: Brain, Behavior, and Immunity - Volume 40, August 2014, Pages 252–268