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The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitonealry twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled [ l4 C]glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP- [l,2-14 C]choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis. (Stroke 1988; 19:217-222) C ytidine 5'-diphosphocholine (CDP-choline, Nicholin) is a key intermediary in the biosynthesis of phosphatidylcholine, 1 an important phospholipid component of cell membranes. CDPcholine is widely employed in Japan and Europe to treat head injury and acute stroke. The therapeutic actions of CDP-choline are thought to be due to restorative effects on phospholipid synthesis in the damaged brain.2 Cerebral ischemia and hypoxia are known to affect membrane composition drastically by increasing free fatty acids (FFAs) 3 and by decreasing phospholipid content.4 -3 In addition, FFAs inhibit oxidative phosphorylation of mitochondrial preparations in vitro.' Arachidonic acid, a major unsaturated FFA released during cerebral ischemia, induces brain edema in vitro 7 and in vivo.8 Recent studies of animal models of cerebral ischemia 910 reveal that CDP-choline attenuates these FFA increases and stimulates resynthesis of phospholipid. CDP-choline also restores the disruption of cerebral mitochondrial lipid metabolism induced by hypoxia.'' These findings strongly suggest the potential usefulness of CDP-choline as a therapeutic agent for treating brain damage induced by cerebral ischemia and hypoxia.We investigated the effects of early CDP-choline treatment of cerebral ischemia on the recovery from From the Biology Laboratories, Central Research Division, Takeda Chemical Industries, Limited, Osaka, Japan.Address for reprints: Mitsuru Kakihana, Biology Laboratories, Central Research Division, ...

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Renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), and sodium and water excretion were measured in anesthetized stroke-prone spontaneously hypertensive rats (SHRSP), spontaneously hypertensive rats (SHR), and control Wistar-Kyoto rats (WKY) at 9 wk of age. Mean arterial pressure in SHRSP and SHR was significantly higher than that in WKY. RBF was slightly increased in SHR and decreased in SHRSP. RVR was markedly elevated only in SHRSP. In both strains of SHR, GFR was significantly increased but water and sodium excretion were similar. When renal perfusion pressure in both strains of SHR was reduced to a level similar to that of WKY by aortic constriction, RBF was slightly but significantly reduced in both SHRSP and SHR, and GFR only in SHRSP. RVR in SHRSP was still higher. Sodium and water excretion were markedly decreased in both SHR and SHRSP. The data suggest that SHRSP are characterized by an alteration in renal hemodynamics at a young age and support the hypothesis that kidneys of SHR require a higher arterial pressure than kidneys of WKY to excrete a given amount of salt and water.