In vivoimaging detects a transient increase in brain arachidonic acid metabolism: a potential marker of neuroinflammation

Abstract

In a rat model of neuroinflammation produced by an intracerebral ventricular infusion of bacterial lipopolysaccaride (LPS), we measured the coefficients of incorporation (k*) of arachidonic acid (AA, 20 : 4n-6) from plasma into each of 80 brain regions, using quantitative autoradiography and intravenously injected [1-(14)C]AA. Compared with control rats infused with artificial cerebrospinal fluid (aCSF), k* was increased significantly in 25 brain areas, many of them close to the CSF compartments, following 6-days of LPS infusion. The increases, ranging from 31 to 76%, occurred in frontal, motor, somatosensory, and olfactory cortex, thalamus, hypothalamus, and septal nuclei, and basal ganglia. Following 28 days of LPS infusion, k* was increased significantly in only two brain regions. Direct analyses of microwaved brain showed that 93 +/- 3 (SD) and 94 +/- 4% of brain radioactivity was in the organic extract as radiolabeled AA in the 6-day control and LPS-infused animals, respectively, compared with 91 +/- 3 and 87 +/- 6% in the 28-day control and LPS-infused animals. These results confirm that brain AA metabolism is disturbed after 6 days of LPS exposure, show this increase is transient, and that these changes can be detected and localized using in vivo imaging with radiolabeled AA.