Effect of cytidine diphosphate choline (CDP-choline) on ischemia-induced alterations of brain lipid in the gerbil

Abstract

Brain ischemia was produced in gerbils (Meriones unguiculatus) by the bilateral ligation of the carotid arteries. Definite changes in the energy status of brain demonstrated that carotid occlusion was effective. Five minutes before ligation, an intraventricular injection of either saline or cytidine disphosphate choline (CDP-choline, 0.6 micromol/brain, 3 microliter) was given to groups of animals. Control animals, with and without CDP-choline, together with the ischemic groups, were decapitated directly into liquid nitrogen; 10 min after arterial ligation. Brain free fatty acids, neutral lipids and phospholipids, which were labeled in vivo by the intraventricular injection of [1-14C]arachidonic acid (0.4-0.6 micro Ci, 6-9 nmol) 2 hr prior to ligation, were extracted, purified, and separated by thin-layer chromatographic procedures. The CDP-choline treatment noticeably corrected the increase of total and individual fatty acids due to ischemia and the increase of their radioactivity content. The changes in neutral lipids, particularly in the diacyl glycerol fraction, were also corrected by the injection of the nucleotide. CDP-choline partially reversed the decreased of brain phosphatidylcholine and of its labeling, which was due to ischemia. All the data indicate that the prior injection of CDP-choline stimulates the choline phosphotransferase reaction of brain towards synthesis of phosphatidylcholine and prevents the release of free fatty acids, particularly of arachidonic acid, associated with ischemia.

Effects of Citicoline on Phospholipid and Glutathione Levels in Transient Cerebral Ischemia

“…16 Pretreatment with citicoline attenuated the loss of PtdCho during ischemia (no reperfusion). 17 We have previously shown that citicoline attenuated arachidonic acid release and partially restored phospholipid loss after ischemia/1-day reperfusion. 9,18 Citicoline can increase the synthesis of PtdCho 8 and sphingomyelin 19,20 and has been shown to prevent the activation of phospholipase A 2 .…”

Effect of Cytidine on Membrane Phospholipid Synthesis in Rat Striatal Slices

“…Various brain diseases, for example, hypoxia, the ischemia related to strokes or injury, and aging per se affect brain levels of these phospholipids (Alberghina et al, 1981a,b ;Goracci et al ., 1981 ;Wie-383 loch et al ., 1984 ;Abe et al ., 1987 ;Abe and Kogure, 1989) . Evidence has been presented that exogenous CDP-choline or CDP-ethanolamine, which are completely degraded to cytidine plus choline or ethanolamine when administered orally, can reverse these membrane changes (Trovarelli et al ., 1981 ;Dorman et al ., 1983) and thereby perhaps ameliorate the clinical findings associated with the disease (De la Morena, 1991) . The present report provides a neurochemical basis for such effects .…”

Pharmacodynamics of citicoline relevant to the treatment of glaucoma

“…Citicoline increases the formation of PtdCho and other phospholipids in brain in vitro as well as in vivo (Lopez-Coviella et al, 1995;Wang and Lee, 2000) and at the same time prevents ischemia-triggered tissue accumulation of FFA (Trovarelli et al, 1981). As discussed in the previous section, these effects should be antiapoptotic and neuroprotective.…”