Microglia are the major cellular source of inducible nitric oxide synthase during experimental herpes encephalitis |
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Authors: | Cristina P Marques Maxim C -J Cheeran Joseph M Palmquist Shuxian Hu James R Lokensgard |
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Institution: | (1) Center for Infectious Diseases and Microbiology Translational Research, Department of Medicine, University of Minnesota, Minnesota, MN, USA |
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Abstract: | Although production of reactive nitrogen and reactive oxygen species (RNS and ROS) is a component of innate defense against
viral infection, their overproduction in the brain may also lead to deleterious consequences. To investigate potential immunopathologic
roles of oxidative stress during herpes encephalitis, the authors examined the expression kinetics of inducible nitric oxide
synthase (iNOS) as well as heme oxygenase-1 (HO-1), a marker of oxidative stress, and evaluated infection-induced oxidative
brain damage. Results from these studies showed that both iNOS and HO-1 gene expression were highly elevated in the brain
within 7 days post infection (d.p.i.) and remained elevated through 21 d.p.i. Real-time bioluminescence imaging of HO-1 promoter-luciferase
transgenic mice confirmed HO-1 promoter activity in the brains of HSV-1-infected animals within 3 d.p.i., which peaked between
5 and 7 d.p.i. Immunohistochemical staining for both 3-nitrotyrosine and 8-hydroxydeoxyguanosine (8-OH-dG), as well as quantitative
assessment of 8-isoprostane levels, demonstrated the presence of viral infection-induced oxidative brain damage. In addition,
when brain leukocytes obtained from animals with experimental herpes encephalitis were sorted using fluorescence-activated
cell sorting (FACS) and the individual cell populations analyzed, CD45(int)/CD11b(+) resident microglia were found to be the
major cellular source of iNOS expression. |
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