Regulation of arachidonic acid metabolism in the perinatal brain during development and under ischemic stress.

Oxygen deprivation following cessation of blood flow to vital organs such as brain, heart, and kidney is a ubiquitous human disease, invariably leading to devastating consequences. Studies in experimental models support the contention that membrane permeability is altered, ion fluxes impaired, and energy stores depleted under these circumstances. Certain lipids such as diglycerides (DG) and arachidonic acid (AA), both of which are important cellular second messengers, appear to increase during ischemia. At this point, the contribution of these and other lipids to cell deregulation, loss of function, and ultimate death has not been clarified because no precise link between lipid alterations as detected in ischemia and subsequent cellular processes has been made. In this report we examine the origin of lipid-derived second messengers in fetal rat brain prelabeled with [3H]AA and study the fate of various lipids upon obstruction of the fetal-maternal circulation. The data support the possibility of a phospholipase A2-mediated deacylation of poly-phosphoinositides (poly-PI) to form free AA and a phospholipase C-mediated hydrolysis of PC to form DG during ischemia.