| Oxygen-sensitive outcomes and gene expression in acute ischemic stroke. | |
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MedLine Citation:
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PMID: 20145654 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Acute ischemic stroke (AIS) results in focal deprivation of blood-borne factors, one of them being oxygen. The purpose of this study was two-fold: (1) to identify therapeutic conditions for supplemental oxygen in AIS and (2) to use transcriptome-wide screening toward uncovering oxygen-sensitive mechanisms. Transient MCAO in rodents was used to delineate the therapeutic potential of normobaric (NBO, 100% O(2), 1ATA) and hyperbaric oxygen (HBO, 100% O(2), 2ATA) during ischemia (iNBO, iHBO) and after reperfusion (rNBO, rHBO). Stroke lesion was quantified using 4.7 T MRI at 48 h. Supplemental oxygen during AIS significantly attenuated percent stroke hemisphere lesion volume as compared with that in room air (RA) controls, whereas identical treatment immediately after reperfusion exacerbated lesion volume (RA=22.4+/-1.8, iNBO=9.9+/-3.6, iHBO=6.6+/-4.8, rNBO=29.8+/-3.6, rHBO=35.4+/-7.6). iNBO and iHBO corrected penumbra tissue pO(2) during AIS as measured by EPR oxymetry. Unbiased query of oxygen-sensitive transcriptome in stroke-affected tissue identified 5,769 differentially expressed genes. Candidate genes were verified by real-time PCR using neurons laser-captured from the stroke-affected somatosensory cortex. Directed microarray analysis showed that supplemental oxygen limited leukocyte accumulation to the infarct site by attenuation of stroke-inducible proinflammatory chemokine response. The findings provide key information relevant to understanding oxygen-dependent molecular mechanisms in the AIS-affected brain. |
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Authors:
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Cameron Rink; Sashwati Roy; Mahmood Khan; Pavan Ananth; Periannan Kuppusamy; Chandan K Sen; Savita Khanna |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-02-10 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 30 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-02 Completed Date: 2010-07-19 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 1275-87 Citation Subset: IM |
Affiliation:
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Department of Surgery, The Ohio State University Medical Center, 473 W. 12th Avenue, Columbus, OH 43210, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Markers / metabolism Brain Ischemia* / metabolism, pathology, therapy Disease Models, Animal Gene Expression Regulation* Humans Hyperbaric Oxygenation* Infarction, Middle Cerebral Artery Leukocytes / cytology, metabolism Mice Mice, Inbred C57BL Nerve Degeneration / metabolism, pathology Oxidative Stress Oxygen / metabolism* Random Allocation Rats Rats, Wistar Stroke* / metabolism, pathology, therapy |
| Grant Support | |
ID/Acronym/Agency:
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NS42617/NS/NINDS NIH HHS; R01 NS042617-07/NS/NINDS NIH HHS; R01 NS042617-08/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 7782-44-7/Oxygen |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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