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-13 (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), 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-γ did not alter COX-2-ir, whereas TNF-α or IL-1β 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-1β, but not TNF-α or INF-γ, 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.