Cerebral insult is associated with a rapid increase in
free fatty acids (FFA) and
arachidonic acid release has been linked to the increase in
eicosanoid biosynthesis. In transient focal
cerebral ischemia induced by middle cerebral artery (MCA) occlusion, there is an inverse relationship between the increase in FFA and the decrease in
ATP, both during the
ischemia period and at later time periods after reperfusion. In this study, the focal
cerebral ischemia model was used to examine incorporation of [14C]
arachidonic acid into the glycerolipids in rat MCA cortex at different reperfusion times after a 60 min
ischemia. The label was injected intracerebrally into left and right MCA cortex 1 hr prior to
decapitation. Labeled
arachidonic acid was incorporated into
phosphatidylcholine,
phosphatidylethanolamine and neutral
glycerides. With increasing time (4-16 hr) after a 60 min
ischemia, an inhibition of labeled arachidonate uptake could be found in the right ischemic MCA cortex, whereas the distribution of radioactivity among the major
phospholipids was not altered. When compared to labeled PC, there was a 3-4 fold increase in incorporation of label into
phosphatidic acid and
triacylglycerols (TG) in the right MCA cortex, suggesting of an increase in de novo biosynthesis of TG. In an in vitro assay system, synaptosomal membranes isolated from MCA cortex 8 and 16 hr after a 60 min
ischemia showed a significant decrease in arachidonoyl transfer to
lysophospholipids, due mainly to a decrease in
lysophospholipid:acylCoA
acyltransferase activity. Assay of
phospholipase A2 activity with both syaptosomes and cytosol, however, did not show differences between left and right MCA cortex or with time after reperfusion. These results suggest that besides
ATP availability, the decrease in
acyltransferase activity may also contribute to the increase in FFA in
cerebral ischemia-reperfusion.