title: Temporal, regional, and cell-specific changes of iNOS expression after intrastriatal microinjection of interferon gamma and bacterial lipopolysaccharide.
abstract: Here we study expression of the inducible isoform of nitric oxide synthases after intrastriatal microinjection of interferon-gamma and bacterial lipopolysaccharide in the rat at different time points to detect time- and localisation-dependent changes of iNOS expression. Three different areas in the striatum and the corpus callosum were evaluated. Antibodies against the glial fibrillary acidic protein and the microglia/brain macrophage epitope ED1 were used to detect colocalization of inducible nitric oxide synthase with astrocytes or activated microglia/brain macrophages, respectively. Inducible nitric oxide synthase-positive cells occurred first in intravascular and perivascular cells at 4 h. Perivascular and parenchymal inducible nitric oxide synthase expression increased up to 24 h in the striatum, whereas in the corpus callosum inducible nitric oxide synthase expression was maximal after 16 h. Inducible nitric oxide synthase was still present in perivascular cells 7 days after immunostimulation. At all time points, inducible nitric oxide synthase was predominantly detected in ED1-positive microglia/brain. Nitrotyrosine immunohistochemistry was performed to detect NO-mediated nitration of proteins at all time points. Nitrotyrosine-positive neurons and microglial cells were detected from 24 h until 7 days after immunostimulation and were absent in controls. Detailed knowledge of the changes in the time course and cellular source of inducible nitric oxide synthase expression following brain immunostimulation provide a basis for establishing treatment strategies and windows of therapeutic intervention during neuroinflammation.
authors.affiliation: Department of Neurology, University of Bonn, Sigmund-Freud Strasse 25, 53105, Bonn, Germany. m.heneka@uni-bonn.de
authors.forename: M T
authors.initials: MT
authors.lastname: Heneka
authors.forename: L
authors.initials: L
authors.lastname: Dumitrescu
authors.forename: P A
authors.initials: PA
authors.lastname: Löschmann
authors.forename: U
authors.initials: U
authors.lastname: Wüllner
authors.forename: T
authors.initials: T
authors.lastname: Klockgether
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D003337:Corpus Callosum / Q000166:cytology; D003342:Corpus Striatum / Q000166:cytology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D017628:Microglia / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D008845:Microinjections; D009443:Neuritis / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; C002744:3-nitrotyrosine; D014443:Tyrosine; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat