Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia
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 intraperitoneally 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 (/sup 14/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-(1,2-/sup 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.
- Research Organization:
- Takeda Chemical Industries, Limited, Osaka (Japan)
- OSTI ID:
- 5208006
- Journal Information:
- Stroke; (United States), Journal Name: Stroke; (United States) Vol. 19:2; ISSN SJCCA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
ALDEHYDES
AMINES
AMMONIUM COMPOUNDS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
BODY
BRAIN
CARBOHYDRATES
CARBON 14 COMPOUNDS
CARDIOVASCULAR DISEASES
CENTRAL NERVOUS SYSTEM
CEREBRAL CORTEX
CEREBRUM
CHOLINE
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
GLUCOSE
HEXOSES
HYDROXY COMPOUNDS
ISCHEMIA
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPOTROPIC FACTORS
MAMMALS
METABOLISM
MONOSACCHARIDES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
QUATERNARY COMPOUNDS
RATS
RODENTS
SACCHARIDES
TRACER TECHNIQUES
VASCULAR DISEASES
VERTEBRATES