title: In vivo expression of cyclooxygenase-2 in rat brain following intraparenchymal injection of bacterial endotoxin and inflammatory cytokines.
abstract: To clarify the role played by prostaglandins in acute brain inflammation we studied the expression of the key enzyme in their formation, cyclooxygenase-2 (COX-2), following microinjection of bacterial endotoxin (LPS), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), in the rat dorsal hippocampus. In spite of the extensive astrocyte and microglial reaction, at 24 hours after LPS injection COX-2 immunoreactivity (COX-2-ir) was exclusively associated with infiltrating neutrophils and with perivascular cells of blood vessels in the area surrounding the injection site. Microinjection of IFN-gamma did not alter COX-2-ir, whereas TNF-alpha or IL-1beta injection induced a moderate COX-2-ir in the perivascular cells of a few blood vessels close to the injection site, and in very few of the infiltrating neutrophils. When IL-1beta, but not TNF-alpha or INF-gamma, was injected in combination with LPS, a strong COX-2-ir was associated with the perivascular cells of most blood vessels in the injected hemisphere and of several of those in the uninjected hemisphere. In addition, COX-2-ir was detected in neutrophils and in several parenchymal cells surrounding the injection site. The parenchymal and perivascular COX-2-positive cells showed a microglia/macrophage-like morphology, as compared with the GSI-B4 isolectin and ED-1 staining, specific for macrophages. Since the constitutive neuronal COX-2 was not affected by any of the conditions studied, the macrophage-like cells found in the perivascular region and in the parenchyma may represent the main source of prostaglandins during focal inflammatory responses in the brain.
authors.affiliation: Laboratory of Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Minghetti
authors.forename: D T
authors.initials: DT
authors.lastname: Walsh
authors.forename: G
authors.initials: G
authors.lastname: Levi
authors.forename: V H
authors.initials: VH
authors.lastname: Perry
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000494:pharmacology*; D004660:Encephalitis / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology; D006624:Hippocampus / Q000201:enzymology* / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D008297:Male; D017628:Microglia / Q000201:enzymology / Q000276:immunology; D008845:Microinjections; D009474:Neurons / Q000201:enzymology / Q000276:immunology; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000096:biosynthesis*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D007527:Isoenzymes; D008070:Lipopolysaccharides; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases