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

Cristina P. Marques, Maxim C Cheeran, Joseph M. Palmquist, Shuxian Hu, James R Lokensgard

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)229-238
Number of pages10
JournalJournal of neurovirology
Issue number3
StatePublished - May 2008

Bibliographical note

Funding Information:
This work was supported by NIH grant MH-066703 and a University of Minnesota Graduate School Doctoral Dissertation Fellowship.


  • HO-1
  • HSV
  • Microglia
  • Oxidative stress
  • iNOS


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