Ischemic brain injury: the importance of calcium, lipolytic activities, and free fatty acids.

Ischemic brain insults are accompanied by several metabolic alterations. In the present review, the adverse reactions, which might be important for the outcome of these insults, are those related to phospholipid and polyunsaturated fatty acid metabolism triggered by the disturbed calcium ion homeostasis in combination with energy depletion following ischemia. The conditions lead to an activation of phospholipases and to a decreased rate of phospholipid resynthesis with a concomitant increase in the concentration of free fatty acids, in particular arachidonic acid. During the recirculation phase, when oxygen supply is reestablished, the polyunsaturated arachidonic acid serves as substrate in the cyclo-oxygenase and lipoxygenase pathways leading to the formation of hydroxy-and hydroperoxy fatty acids, prostaglandins and possibly also leukotrienes. These substances have adverse effects on the integrity of cell membranes, irreversibly altering the functional properties of the cells, and also vasomodulator properties influencing the effectiveness of the reperfusion of the brain.