Document Detail


Anti-apoptotic effect of granulocyte-colony stimulating factor after focal cerebral ischemia in the rat.
MedLine Citation:
PMID:  17084035     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the molecular mechanisms of the anti-apoptotic properties of granulocyte-colony stimulating factor (G-CSF) on neurons and whether G-CSF affects glial cell survival following focal cerebral ischemia in rats. Sprague-Dawley rats were subjected to a transient 90 min middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. Rats were treated with either a single dose of G-CSF (50 microg/kg, s.c.) at the onset of reperfusion or G-CSF (50 microg/kg body weight, s.c.) was administered starting at the onset of reperfusion and followed by the administration of the same dose per day for an additional 2 days. Brains were harvested either 24 h, 72 h or 2 weeks after reperfusion for assays of infarct volume, immunohistological studies and Western blot analysis for phosphorylated signal transducer and activator of transcription 3 (pSTAT3), Pim-1, bcl-2, Bax, cytochrome c, cellular inhibitor of apoptosis protein 2 (cIAP2), and cleaved caspase-3 levels. G-CSF significantly reduced infarct volume and ameliorated the early neurological outcome. G-CSF treatment significantly up-regulated pSTAT3, Pim-1, bcl-2 expression, and down-regulated cytochrome c release to the cytosol, Bax translocation to the mitochondria, and cleaved caspase-3 levels in neurons. The activation of the STAT3 pathway was accompanied by increased cIAP2 expression in glial cells. After MCAO, G-CSF treatment increased both neuronal and glial survival by effecting different anti-apoptotic pathways which reflects the multifactorial actions of this drug. These changes were associated with remarkable improvement in tissue preservation and behavioral outcome.
Authors:
I Solaroglu; T Tsubokawa; J Cahill; J H Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-11-02
Journal Detail:
Title:  Neuroscience     Volume:  143     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-04     Completed Date:  2007-02-23     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  965-74     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*,  physiology
Apoptosis Regulatory Proteins / drug effects,  metabolism
Brain Ischemia / drug therapy*,  metabolism,  physiopathology
Cell Survival / drug effects,  physiology
Cerebral Infarction / drug therapy*,  metabolism,  physiopathology
Disease Models, Animal
Down-Regulation / drug effects,  physiology
Drug Administration Schedule
Granulocyte Colony-Stimulating Factor / pharmacology*,  therapeutic use
Infarction, Middle Cerebral Artery / drug therapy,  metabolism,  physiopathology
Male
Neuroglia / drug effects,  metabolism
Neurons / drug effects,  metabolism
Neuroprotective Agents / pharmacology*,  therapeutic use
Protein Transport / drug effects,  physiology
Rats
Rats, Sprague-Dawley
Reperfusion Injury / drug therapy,  metabolism,  physiopathology
Signal Transduction / drug effects,  physiology
Treatment Outcome
Up-Regulation / drug effects,  physiology
Grant Support
ID/Acronym/Agency:
HD43120/HD/NICHD NIH HHS; NS43338/NS/NINDS NIH HHS; NS45694/NS/NINDS NIH HHS; NS53407/NS/NINDS NIH HHS; R01 HD043120/HD/NICHD NIH HHS; R01 HD043120-03/HD/NICHD NIH HHS; R01 NS043338/NS/NINDS NIH HHS; R01 NS043338-03/NS/NINDS NIH HHS; R01 NS045694/NS/NINDS NIH HHS; R01 NS045694-04/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Neuroprotective Agents; 143011-72-7/Granulocyte Colony-Stimulating Factor
Comments/Corrections

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