THE EFFECTS OF PROLONGED TREATMENT WITH CITICOLINE IN TEMPORARY EXPERIMENTAL FOCAL ISCHEMIA

Potential therapeutic effects of cytidine 5-diphosphocholine (citicoli ne), a key intermediary in the biosynthesis of the membrane phospholip id, phosphatidylcholine, are presumably related to enhanced phospholip id synthesis in the ischemic brain. We evaluated prolonged citicoline treatment in a temporary focal ischemia model. Using the suture occlus ion model, we induced 2 hours of temporary ischemia in 30 Sprague-Dawl ey rats. The rats were randomly and blindly assigned to receive intrap eritoneally 500 mg/kg citicoline (HD), 100 mg/kg citicoline (LD) or ph ysiologic saline as the control group once daily for 7 days (n = 10 pe r group) beginning at the time of reperfusion. Neurological scoring (0 -5 scale) was performed daily. After elective sacrifice on day 7, or e arlier if death occured prematurely, the brains underwent 2,3,5-triphe nyltetrazolium chloride (TTC) staining for calculation of corrected in farct and edema volume. The mean corrected infarct volume in the HD gr oup was 125 +/- 45.2 mm(3) (mean +/- SD), significantly smaller than c ontrols, mm 243.5 +/- 88.6 mm(3) (p < 0.01, Scheffe's-test). The LD gr oup infarct volume was 200.2 +/- 62.8 mm(3) (N.S.). The mean amount of brain 3 edema in the HD group was 46.4 +/- 45.6 mm(3) was smaller tha n the controls, 92.3 +/- 54.4 mm(3) and the LD group, 84.9 +/- 71.7 mm (3) (N.S.). Mortality before day 7 in the HD was 30% while it was 50% in the two other groups. The neurologic score on day 7 was 2.5 +/- 1.8 in the HD group, 3.3 +/- 1.8 in the LD group and 3.4 +/- 1.7 in contr ols (N.S.). These results demonstrate that extended high dose citicoli ne treatment significantly reduced infarct volume in this temporary fo cal ischemia model and that there was a trend toward reducing brain ed ema and mortality. These effects may be related to membrane stabilizat ion and inhibition of free fatty acid release.