| Anti-apoptotic effect of granulocyte-colony stimulating factor after focal cerebral ischemia in the rat. | |
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MedLine Citation:
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PMID: 17084035 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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I Solaroglu; T Tsubokawa; J Cahill; J H Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-11-02 |
Journal Detail:
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Title: Neuroscience Volume: 143 ISSN: 0306-4522 ISO Abbreviation: Neuroscience Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-12-04 Completed Date: 2007-02-23 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 7605074 Medline TA: Neuroscience Country: United States |
Other Details:
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Languages: eng Pagination: 965-74 Citation Subset: IM |
Affiliation:
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Department of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, CA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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HD43120/HD/NICHD NIH HHS; NS43338/NS/NINDS NIH HHS; NS45694/NS/NINDS NIH HHS; NS53407/NS/NINDS NIH HHS; R01 HD043120-03/HD/NICHD NIH HHS; R01 NS043338-03/NS/NINDS NIH HHS; R01 NS045694-04/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/Neuroprotective Agents; 143011-72-7/Granulocyte Colony-Stimulating Factor |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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