Biochemical Events in the Ischemic Brain and Pharmacological Basis of Mannitol, Vitamin E, Glucocorticoid, and Phenytoin
Brain cell membranes are relatively enriched in polyphosphoinositides (PPI) which contain large amounts of arachidonic acid and stearic acid. Ischemia gives rise to severe energy depletion and the decomposition of PPI into diglyceride and inositol triphosphate by activation of phospholipase C. The subsequent hydrolysis of diglyceride accounts for free fatty acid (FFA) accumulation in the early stage of ischemia. Other general phospholipids are also hydrolyzed into lysophospholipids and FFA by activation of phospholipase A2 with an increase of Ca2+. On the other hand, free radical reaction is thought to be caused by active oxygens in the fatty acid carbon chain of phospholipids during ischemia, and is enhanced by Ca2+ which is mobilized by inositol triphosphate. The accumulated FFA in the ischemia is consumed as a substrate for propagation of free radical mediated peroxidation in the reperfusion period. This paper tries to attract attention to the PPI metabolism as a trigger of ischemic cell damage and participation of free radicals in the propagation of membrane lipid peroxidation. A study of preventive methods against the above pathophysiology was also made in the administration of mannitol, vitamin E, glucocorticoid, and phenytoin.
KeywordsHigh Performance Liquid Chromatography Electron Spin Resonance Ischemic Brain Free Radical Reaction Electron Spin Resonance Measurement
Unable to display preview. Download preview PDF.
- 2.Imaizumi S, Suzuki J, Tominaga T, Uenohara H, Yoshimoto T (1985) Effect of free radical scavengers on cerebral ischemia and hypoxia evaluated by chemiluminescence. In: Spetzler RF (ed) Cerebral revascularization for stroke. Thieme-Stratton, New York, pp 299–306Google Scholar
- 6.Tominaga T, Imaizumi S, Yoshimoto T, Suzuki J, Fujita Y (in press) Application of spin trapping study to NADPH-dependent lipid peroxidation in rat ischemic brain homogenate. Brain ResGoogle Scholar