In vivo imaging detects a transient increase in brain arachidonic acid metabolism: a potential marker of neuroinflammation.
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.
Lee
Helen
H
Brain Physiology and Metabolism Section, National Institutes on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Villacreses
Nelly E
NE
Rapoport
Stanley I
SI
Rosenberger
Thad A
TA
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D001345:Autoradiography; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D004195:Disease Models, Animal; D018450:Disease Progression; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis / Q000097:blood; D051381:Rats; D013997:Time Factors
D015415:Biomarkers; D002250:Carbon Radioisotopes; D008055:Lipids; D016718:Arachidonic Acid