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Nitric Oxide Protects against Infection-Induced Neuroinflammation by Preserving the Stability of the Blood-Brain Barrier

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dc.contributor.authorGabriela C. Oliveraen_US
dc.contributor.authorXiaoyuan Renen_US
dc.contributor.authorSuman K. Vodnalaen_US
dc.contributor.authorJun Luen_US
dc.contributor.authorLucia Coppoen_US
dc.contributor.authorChaniya Leepiyasakulchaien_US
dc.contributor.authorArne Holmgrenen_US
dc.contributor.authorKrister Kristenssonen_US
dc.contributor.authorMartin E. Rottenbergen_US
dc.contributor.otherMahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technologyen_US
dc.date.accessioned2016-04-20T08:58:15Z
dc.date.accessioned2017-06-20T16:43:10Z
dc.date.available2016-04-20T08:58:15Z
dc.date.available2017-06-20T16:43:10Z
dc.date.issued2016-02
dc.description.abstractNitric oxide (NO) generated by inducible NO synthase (iNOS) is critical for defense against intracellular pathogens but may mediate inflammatory tissue damage. To elucidate the role of iNOS in neuroinflammation, infections with encephalitogenic Trypanosoma brucei parasites were compared in inos-/- and wild-type mice. Inos-/- mice showed enhanced brain invasion by parasites and T cells, and elevated protein permeability of cerebral vessels, but similar parasitemia levels. Trypanosome infection stimulated T cell- and TNF-mediated iNOS expression in perivascular macrophages. NO nitrosylated and inactivated pro-inflammatory molecules such as NF-κΒp65, and reduced TNF expression and signalling. iNOS-derived NO hampered both TNF- and T cell-mediated parasite brain invasion. In inos-/- mice, TNF stimulated MMP, including MMP9 activity that increased cerebral vessel permeability. Thus, iNOS-generated NO by perivascular macrophages, strategically located at sites of leukocyte brain penetration, can serve as a negative feed-back regulator that prevents unlimited influx of inflammatory cells by restoring the integrity of the blood-brain barrier.en_US
dc.identifier.citationPlos One. Vol.12, No.2 (2016), e1005442en_US
dc.identifier.urihttps://hdl.handle.net/20.500.14594/2134
dc.language.isoengen_US
dc.subjectOpen Access articleen_US
dc.titleNitric Oxide Protects against Infection-Induced Neuroinflammation by Preserving the Stability of the Blood-Brain Barrieren_US
dc.typeArticleen_US
dspace.entity.typePublication
mods.location.urlhttp://www.ncbi.nlm.nih.gov/pubmed/26915097
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