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.

Bacterial lipopolysaccharide induces a dose-dependent activation of neuroglia and loss of basal forebrain cholinergic cells in the rat brain

“…These studies show that LPS infusion resulted in a linear and dose-dependent increase in the percentage of reactive neuroglia within the brain and that moderate to high doses of LPS (5.0–500 ng/hr) were necessary to decrease the number of ChAT-positive cells in the basal forebrain. These results suggest that the selective increase in the metabolism of brain ARA using a low dose rate of LPS reflects primarily neuroglia activation, which is consistent with regional increases in ARA incorporation as determined by autoradiographic analysis [2] .…”

Dietary α‐linolenic acid increases brain but not heart and liver docosahexaenoic acid levels

“…It is well established that an increase in n-3 dietary PUFA leads to a decrease in n-6 PUFA tissue content, because these two families of EFA compete for the same set of enzymes (59). Decreased n-6 levels are considered beneficial because 20:4n-6 and its cyclooxygenase metabolites are related to the onset of different diseases, such as atherosclerosis (60) and inflammation (61)(62)(63), and the promotion of tumor proliferation (64). Nevertheless, all the beneficial effects associated with 22:6n-3-and 20:5n-3-enriched diets have overshadowed the importance of 20:4n-6 in general physiological functioning.…”

Chronic Lithium Chloride Administration to Unanesthetized Rats Attenuates Brain Dopamine D2-Like Receptor-Initiated Signaling Via Arachidonic Acid

“…In a rat model of neuroinflammation, elevated baseline values for k* correlate with increased activities of cPLA 2 and sPLA 2 but not iPLA 2 , as well as increased turnover of AA within brain phospholipids (Lee et al, 2004;Rosenberger et al, 2004). These correlations suggest that the elevated baseline values for k* in brain visual and auditory regions in LiCl fed rats (Table 2) also reflect increased PLA 2 activity and increased AA turnover, possibly due to increased retinal and cochlear inputs, respectively, to these regions (Jung and Reme, 1994;Pfeilschifter et al, 1988).…”