Minghetti, L., Walsh, D.T., Levi, G. and Perry, V.H.
In vivo expression of cyclooxygenase-2 in rat brain following intraparenchymal injection of bacterial endotoxin and inflammatory cytokines
Journal of Neuropathology & Experimental Neurology, 58, (11), .
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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-1 (3 (IL-I[beta]), tumor necrosis factor-a (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-7 did not alter COX-2-ir, whereas TNF-[alpha] or IL-I[beta] 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 ILI[beta], 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.
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