title: Inducible nitric oxide synthase in Theiler's murine encephalomyelitis virus infection.
abstract: We investigated the role of inducible nitric oxide synthase (iNOS) in Theiler's murine encephalomyelitis virus (TMEV) infection of susceptible (SJL) and resistant (C57BL/6 [B6]) strains of mice. TMEV is an excellent model of virus-induced demyelinating disease, such as multiple sclerosis (MS). Previous studies of others have suggested that NO may play a role in the pathogenesis of demyelinating disease. The presence and level of iNOS were determined in the brains and spinal cords of SJL and B6 TMEV-infected mice by the following methods: (i) PCR amplification of iNOS transcripts, followed by Southern blotting with an iNOS-specific probe, and (ii) immunohistochemical staining with an anti-iNOS-specific affinity-purified rabbit antibody. iNOS-specific transcripts were determined in the brains and spinal cord of both SJL and B6 TMEV-infected mice on days 0 (control), days 3, 6, and 10 (encephalitic stage of disease), and days 39 to 42, 66, and 180 (demyelinating phase) postinfection (p.i.). iNOS-specific transcripts were found in the brains and spinal cords of both SJL and B6 TMEV-infected mice at 6, 10, and 39 (SJL) days p.i., but they were absent in mock-infected mice and in TMEV-infected SJL and B6 mice at 0, 3, 66, and 180 days p.i. Immunohistochemical staining confirmed the presence of iNOS protein in both TMEV-infected SJL and B6 mice at days 6 and 10 p.i., but not at days 0, 3, 66, and 180 days p.i. Weak iNOS staining was also observed in TMEV-infected SJL mice at 42 days p.i. iNOS-positive staining was found in reactive astrocytes surrounding areas of necrotizing inflammation, particularly in the midbrain. Weak iNOS staining was also observed in cells of the monocyte/macrophage lineage in areas of parenchymal inflammation and necrosis (mesencephalon) and in leptomeningeal and white matter perivascular infiltrates of the spinal cord. Rod-shaped microglia-like cells and foamy macrophages (myelin-laden) were iNOS negative. These results suggest that NO does not play a direct role in the late phase of demyelinating disease in TMEV-infected mice.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19106, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Oleszak
authors.forename: C D
authors.initials: CD
authors.lastname: Katsetos
authors.forename: J
authors.initials: J
authors.lastname: Kuzmak
authors.forename: A
authors.initials: A
authors.lastname: Varadhachary
mesh_terms: D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology; D003711:Demyelinating Diseases / Q000201:enzymology / Q000821:virology; D004790:Enzyme Induction; D005260:Female; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D011051:Poliomyelitis / Q000201:enzymology* / Q000473:pathology; D011817:Rabbits; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology; D017945:Theilovirus / Q000502:physiology*
chemical_list: D019001:Nitric Oxide Synthase