CYCLOOXYGENASE-2 MESSENGER-RNA EXPRESSION IN RAT-BRAIN AFTER PERIPHERAL INJECTION OF LIPOPOLYSACCHARIDE

Inducible cyclooxygenase 2 (COX 2) converts arachidonic acid to prosta glandins, which are thought to mediate various peripheral Lipopolysacc haride (LPS)-induced central effects, including generation of fever an d activation of the hypothalamic-pituitary-adrenal axis. To localize p rostaglandin production in the brain following peripheral LPS administ ration, COX 2 mRNA expression was examined by in situ hybridization hi stochemistry in rats injected intraperitoneally (i.p.) or intravenousl y (i.v.) with various doses of LPS or saline. Constitutive expression of COX 2 mRNA was found in neurons of cortex, hippocampus, and amygdal a, but not in cells of the blood vessels. COX 2 mRNA levels were not a ltered in saline-injected animals as compared to non-injected controls . In LPS-injected animals, no consistent changes of neuronal COX 2 mRN A expression were observed. COX 2 mRNA expression appeared ex novo at 0.5-h post-injection in cells closely associated with blood vessels, h owever, ex novo labeling of the number of labeled cells increased to a peak at 2 h and subsided gradually to basal levels by 24 h. Initially , labeling was observed in cells comprising major surface-lying blood vessels and meninges. Later, vascular and perivascular cells associate d with smaller penetrating blood vessels were labeled. This pattern of COX 2 mRNA induction is independent of the route and dose of the LPS injection. The induced COX 2 mRNA producing cells are identified as en dothelial and leptomeningeal cells. Changes in COX 2 mRNA expression w ere not observed in circumventricular organs. These results suggest th at peripheral LPS induces a rapid increase in COX 2 production through out the vasculatures of the brain, which could affect the neuronal act ivity of widespread brain regions by elevating the levels of prostagla ndins. (C) 1998 Elsevier Science B.V. All rights reserved.