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Citicoline mechanisms and clinical efficacy in cerebral ischemia.
- Source :
-
Journal of neuroscience research [J Neurosci Res] 2002 Oct 15; Vol. 70 (2), pp. 133-9. - Publication Year :
- 2002
-
Abstract
- Citicoline, an intermediate in the biosynthesis of phosphatidylcholine (PtdCho), has shown beneficial effects in various CNS injury models and neurodegenerative diseases. PtdCho hydrolysis by phospholipase A(2) (PLA(2)) after cerebral ischemia and reperfusion yields arachidonic acid (ArAc) and lyso-PtdCho. ArAc oxidative metabolism results in formation of reactive oxygen species and lipid peroxides. Lyso-PtdCho could inhibit activity of cytidine triphosphate-phosphocholine cytidylyltransferase (the rate-limiting enzyme in PtdCho biosynthesis), resulting in impaired PtdCho synthesis. Citicoline significantly increased glutathione levels and attenuated release of ArAc and the loss of PtdCho, cardiolipin, and sphingomyelin following transient cerebral ischemia. These effects could be explained by an effect of citicoline on PLA(2). Based on these observations, a mechanism has been hypothesized. This Mini-Review summarizes recent experimental data on the effects of citicoline in cerebral ischemia and evaluates several factors that might have hindered efficacy of citicoline in stroke clinical trials in the United States. Clinical stroke trials of citicoline in Europe and Japan have demonstrated beneficial effects. U.S. trials shown only marginal effects, which might be due to the 24 hr time window, the dose and route of administration, and the stringency of the primary outcome parameters. Recent evaluation of U.S. clinical data suggests that reduction of infarct growth may be a more sensitive measure of the citicoline effect than improvement on the NIH Stroke Scale (NIHSS) by > or =7 points. The citicoline neuroprotective mechanism has not been clearly identified, and its potential in stroke treatment might still be fully recognized in the United States. The clinical efficacy of citicoline should be examined further in light of the recent phase III stroke clinical trials and experimental data for cerebral ischemia.<br /> (Copyright 2002 Wiley-Liss, Inc.)
- Subjects :
- Animals
Arachidonic Acid metabolism
Brain Ischemia metabolism
Clinical Trials as Topic
Disease Models, Animal
Humans
Ischemic Attack, Transient drug therapy
Ischemic Attack, Transient metabolism
Phosphatidylcholines metabolism
Phospholipases A drug effects
Phospholipases A metabolism
Rats
Treatment Outcome
Brain Ischemia drug therapy
Cytidine Diphosphate Choline pharmacology
Cytidine Diphosphate Choline therapeutic use
Neuroprotective Agents pharmacology
Neuroprotective Agents therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0360-4012
- Volume :
- 70
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of neuroscience research
- Publication Type :
- Academic Journal
- Accession number :
- 12271462
- Full Text :
- https://doi.org/10.1002/jnr.10403