title: Appearance of inducible nitric oxide synthase in the rat central nervous system after rabies virus infection and during experimental allergic encephalomyelitis but not after peripheral administration of endotoxin.
abstract: The cellular localization of inducible (iNOS) and constitutive (cNOS) nitric oxide synthase was studied in rats by immunocytochemical techniques involving specific iNOS and cNOS directed antibodies and by NADPH-diaphorase histochemistry. Paraformaldehyde-fixed vibratome sections of brains and cryostat sections of peripheral lymph nodes were studied of rats treated with endotoxin (2.5 micrograms/kg or 2.5 mg/kg i.v.), rats infected with rabies virus, and rats exposed to experimental allergic encephalomyelitis (EAE). Endotoxin-treated animals showed no appearance of immunoreactive iNOS (ir-iNOS) cells in the brain with the exception of a few microglial cells near the median eminence and some meningeal macrophages. In the same animals however, iNOS-immunoreactive cells were found in peripheral lymph nodes. Neurons that stain positive for cNOS and for NADPH-diaphorase could be observed in brains of control as well as of endotoxin-treated animals with a similar distribution and staining intensity. In contrast, animals that had been infected with rabies virus or subjected to EAE, showed the appearance of ir-iNOS-positive cells in several brain areas. These cells are located near blood vessels and lesion sites. The majority of these cells are GSA-I-B4 isolectin-positive and therefore are likely to represent macrophages. Our data suggest that increased production of nitric oxide may play a role in the altered brain functions in rabies-infected and EAE rats. On the contrary, increased nitric oxide production is probably not involved in the non-specific symptoms of sickness induced by endotoxin.
authors.affiliation: Department of Pharmacology, Research Institute Neurosciences Free University, Faculty of Medicine, Amsterdam, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Van Dam
authors.forename: J
authors.initials: J
authors.lastname: Bauer
authors.forename: W K
authors.initials: WK
authors.lastname: Man-A-Hing
authors.forename: C
authors.initials: C
authors.lastname: Marquette
authors.forename: F J
authors.initials: FJ
authors.lastname: Tilders
authors.forename: F
authors.initials: F
authors.lastname: Berkenbosch
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D002490:Central Nervous System; D004679:Encephalomyelitis / Q000276:immunology / Q000473:pathology*; D004731:Endotoxins / Q000633:toxicity*; D007150:Immunohistochemistry; D007239:Infections; D008297:Male; D009252:NADPH Dehydrogenase; D009569:Nitric Oxide / Q000378:metabolism*; D011818:Rabies; D051381:Rats
chemical_list: D000906:Antibodies; D004731:Endotoxins; D009569:Nitric Oxide; D009252:NADPH Dehydrogenase