Ischemic brain damage: focus on lipids and lipid mediators.
The last two decades of research have produced detailed information not only on how ischemia causes degradation of phospholipids and accumulation of potentially cytotoxic breakdown products of such lipids, but also on reactions elicited by the subsequent conversion of these products into a series of lipids, mediating an array of cellular and intercellular reactions. It now seems clear that PAF, as well as several of the cyclooxygenase and lipoxygenase products of arachidonic acid, can induce changes, particularly in the microvasculature, which jeopardize cell survival in reperfused tissue. It is equally clear that, at least following long periods of ischemia, free radicals generated in reactions that are interacting with those producing eicosanoids and PAF play a similar role. A somewhat more speculative mechanism links sustained activation and membrane translocation of PKC to delayed neuronal death following transient ischemia. All of these interactions underscore the importance of lipolytic events for cell damage in ischemia and other conditions with a compromised cellular energy metabolism.
Siesjö
B K
BK
Department of Neurobiology, University Hospital S-221, Lund, Sweden.
Katsura
K
K
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism; D050356:Lipid Metabolism; D008066:Lipolysis
D001095:Arachidonic Acids; D005230:Fatty Acids, Nonesterified; D005609:Free Radicals; D002118:Calcium