Microglia are the major cellular source of inducible nitric oxide synthase during experimental herpes encephalitis

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...

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Bibliographic Details
Published in:Journal of neurovirology 2008-01, Vol.14 (3), p.229-238
Main Authors: Marques, Cristina P, Cheeran, Maxim C-J, Palmquist, Joseph M, Hu, Shuxian, Lokensgard, James R
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Brain - immunology
Brain - metabolism
Brain - pathology
CD11b Antigen - analysis
CD11b Antigen - biosynthesis
Dinoprost - analogs & derivatives
Dinoprost - metabolism
Encephalitis, Herpes Simplex - immunology
Encephalitis, Herpes Simplex - metabolism
Encephalitis, Herpes Simplex - pathology
Flow Cytometry
Heme Oxygenase-1 - biosynthesis
Heme Oxygenase-1 - genetics
Herpesvirus 1, Human
Human viral diseases
Immunology
Infectious Diseases
Leukocyte Common Antigens - analysis
Leukocyte Common Antigens - biosynthesis
Leukocytes - immunology
Leukocytes - metabolism
Luciferases - genetics
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Transgenic
Microglia - immunology
Microglia - metabolism
Neurology
Neurosciences
Nitric Oxide Synthase Type II - biosynthesis
Nitric Oxide Synthase Type II - genetics
Oxidative Stress
Polymerase Chain Reaction
Promoter Regions, Genetic
RNA, Messenger - genetics
Time Factors
Viral diseases
Viral diseases of the nervous system
Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye
Virology
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Summary: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.
ISSN:1355-0284
1538-2443
DOI:10.1080/13550280802093927