Membrane lipids in the pathogenesis of brain edema: phospholipids and arachidonic acid, the earliest membrane components changed at the onset of ischemia.

This chapter reviews studies concerning cellular membranes in the pathogenesis of cerebral edema. The main topics discussed are membrane lipids and the observation that the concentration of endogenous free fatty acids increases rapidly and reversibly in the brain after a single electroconvulsive shock. This change suggests that an active deacylation takes place. In addition, brief periods of ischemia trigger a strikingly high production of free fatty acids not from triacylglycerol breakdown but likely arising from membrane lipids. Since cellular membrane damage takes place during the early stages of edema either in neural or endothelial cells, the described changes may be involved in the pathogenesis of brain edema. The free fatty acid production is a unique property of the mature brains of rat, mouse, and monkey. It predominates in gray matter as compared to white matter. The rate of production during early ischemia is comparable to that observed in adipose tissue under maximal hormonal stimulation. In newborn mammalians, as in brains of mature poikilotherms, rates of production during early ischemia are low. The involvement of inositol lipids in the process is suggested since stearic and arachidonic acid are not only produced as free fatty acids but are also acylated in diacylglycerol during the first few minutes of rat and mouse brain ischemia. Prostaglandins and their metabolites of free arachidonic acid, at least during the first 4 to 5 min of ischemia when the rate of production is linear. Harmful membrane effects of lipid peroxides are also discussed.