Document Detail


CDP-choline: neuroprotection in transient forebrain ischemia of gerbils.
MedLine Citation:
PMID:  10561698     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CDP-choline is a rate-limiting intermediate in the biosynthesis of phosphatidylcholine (PtdCho), an important component of the neural cell membrane. The ability of CDP-choline to alter phospholipid metabolism is an important function in the treatment of ischemic injury. Exogenous treatment with CDP-choline stimulates PtdCho synthesis and prevents release of free fatty acids (FFA), especially arachidonic acid (AA), after ischemia/reperfusion. Phase III clinical trials of CDP-choline in the treatment of stroke are currently underway. Here we report the neuroprotection by CDP-choline in transient forebrain ischemia of gerbils. CDP-choline significantly attenuated the blood-brain barrier (BBB) dysfunction after ischemia with 6-hr reperfusion, and considerably reduced the increase of AA in FFA and leukotriene C(4) (LTC(4)) synthesis at 1 day. Edema was significantly elevated after 1 and 2 days, but attained maximum at 3-day reperfusion. CDP-choline substantially attenuated edema at 3 days. Ischemia resulted in 80 +/- 8% CA(1) hippocampal neuronal death after 6-day reperfusion, and CDP-choline provided 65 +/- 6% neuroprotection. CDP-choline may act by increasing PtdCho synthesis via two pathways: (1) conversion of 1, 2-diacylglycerol to PtdCho, and (2) biosynthesis of S-adenosyl-L-methionine, thus stabilizing the membrane and reducing AA release and metabolism to leukotriene C(4). This would result in decreased toxicity due to AA, leukotrienes, oxygen radicals, lipid peroxidation, and altered glutamate uptake, thus limiting BBB dysfunction, edema and providing neuroprotection.
Authors:
A M Rao; J F Hatcher; R J Dempsey
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  58     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-01-05     Completed Date:  2000-01-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  697-705     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Wiley-Liss, Inc.
Affiliation:
Department of Neurological Surgery, University of Wisconsin, Madison, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arachidonic Acid / metabolism
Blood-Brain Barrier / drug effects
Cerebrovascular Circulation / physiology
Cytidine Diphosphate Choline / pharmacology*
Gerbillinae
Hippocampus / drug effects,  pathology
Ischemic Attack, Transient / drug therapy*,  physiopathology
Leukotriene C4 / metabolism
Neurons / drug effects
Neuroprotective Agents / pharmacology*
Phosphatidylcholines / metabolism
Prosencephalon / physiopathology*
Grant Support
ID/Acronym/Agency:
P01 NS31220/NS/NINDS NIH HHS; R01 NS 28000/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Neuroprotective Agents; 0/Phosphatidylcholines; 506-32-1/Arachidonic Acid; 72025-60-6/Leukotriene C4; 987-78-0/Cytidine Diphosphate Choline

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


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