Effects of citicoline on phospholipid and glutathione levels in transient cerebral ischemia

Background and Purpose-Cytidine-5'-diphosphocholine (citicoline or CDP-chol ine) is an essential intermediate in the biosynthesis of phosphatidylcholin e, an important component of the neural cell membrane. Citicoline provided significant neuroprotection after transient forebrain ischemia in gerbils. This study was undertaken to examine changes and effects of citicoline on p hospholipids and glutathione synthesis after transient cerebral ischemia an d reperfusion. Methods-Ten-minute transient forebrain ischemia was induced by bilateral ca rotid artery occlusion in male Mongolian gerbils with reperfusion up to 6 d ays. Citicoline (500 mg/kg IP in saline) was given to gerbils just after th e end of ischemia, at 3-hour reperfusion, and daily thereafter until I day before euthanasia. Hippocampal lipids were extracted and analyzed by thin-l ayer and gas chromatography. Glutathione was measured by using an enzymatic recycling assay. Glutathione reductase activity was determined by measurin g NADPH oxidation. Results-Significant decreases in phospholipids occurred at 1-day reperfusio n. Citicoline significantly restored the phosphatidylcholine, sphingomyelin , and cardiolipin levels but did not affect phosphatidylinositol and phosph atidylserine at 1 day. The phospholipids returned to sham levels over days 2 to 6 and were unaffected by citicoline. Ceramide levels significantly inc reased by 3 and 6 days of reperfusion and were unaltered by citicoline. Isc hemia resulted in significant decreases in glutathione and glutathione redu ctase activity over 3 days of reperfusion. Citicoline significantly increas ed total glutathione and glutathione reductase activity and decreased the g lutathione oxidation ratio, an indicator of glutathione redox status. Conclusions-Our data indicated that the effects of citicoline on phospholip ids occurred primarily during the first day of reperfusion, with effects on glutathione being important over the 3-day reperfusion period.