Document Detail


Citicoline decreases phospholipase A2 stimulation and hydroxyl radical generation in transient cerebral ischemia.
MedLine Citation:
PMID:  12868064     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neuroprotection by citicoline (CDP-choline) in transient cerebral ischemia has been demonstrated previously. Citicoline has undergone several Phase III clinical trials for stroke, and is being evaluated for treatment of Alzheimer's and Parkinson's diseases. Phospholipid degradation and generation of reactive oxygen species (ROS) are major factors causing neuronal injury in CNS trauma and neurodegenerative diseases. Oxidative metabolism of arachidonic acid (released by the action of phospholipases) contributes to ROS generation. We examined the effect of citicoline on phospholipase A(2) (PLA(2)) activity in relation to the attenuation of hydroxyl radical (OH.) generation after transient forebrain ischemia of gerbil. PLA(2) activity (requires mM Ca(2+)) increased significantly (P < 0.05) in both membrane (50.2 +/- 2.2 pmol/min/mg protein compared to sham 35.9 +/- 3.2) and mitochondrial fractions (77.0 +/- 1.2 pmol/min/mg protein compared to sham 33.9 +/- 1.2) after cerebral ischemia and 2 hr reperfusion in gerbil, which was significantly attenuated (P < 0.01) by citicoline (membrane, 39.9. +/- 2.2 and mitochondria, 41.9 +/- 3.2 pmol/min/mg protein). In vitro, citicoline and its components cytidine and choline had no effect on PLA(2) activity, and thus citicoline as such is not a PLA(2) inhibitor. Ischemia/reperfusion resulted in significant OH. generation (P < 0.01) and citicoline significantly (P < 0.01) attenuated their formation (expressed as 2,3-dihydroxybenzoic acid/salicylate ratio; ischemia/24 hr reperfusion, 6.30 +/- 0.23; sham, 2.56 +/- 0.27; ischemia/24 hr reperfusion + citicoline, 4.85 +/- 0.35). These results suggest that citicoline affects PLA(2) stimulation and decreases OH. generation after transient cerebral ischemia.
Authors:
Rao Muralikrishna Adibhatla; James F Hatcher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  73     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-07-17     Completed Date:  2003-09-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  308-15     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Wiley-Liss, Inc.
Affiliation:
Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin 53792-3232, USA. adibhatl@neurosurg.wisc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / metabolism
Cell Death / drug effects
Cytidine Diphosphate Choline / pharmacology*
Gerbillinae
Hippocampus / metabolism,  pathology
Hydroxyl Radical / metabolism
Ischemic Attack, Transient / drug therapy*,  metabolism*,  pathology
Lipid Peroxidation / drug effects
Male
Neurons / metabolism,  pathology
Neuroprotective Agents / pharmacology
Nootropic Agents / pharmacology*
Phospholipases A / metabolism*
Phospholipases A2
Chemical
Reg. No./Substance:
0/Neuroprotective Agents; 0/Nootropic Agents; 3352-57-6/Hydroxyl Radical; 7440-70-2/Calcium; 987-78-0/Cytidine Diphosphate Choline; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Phospholipases A2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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