Document Detail

Mechanisms contributing to cerebral infarct size after stroke: gender, reperfusion, T lymphocytes, and Nox2-derived superoxide.
MedLine Citation:
PMID:  20145655     Owner:  NLM     Status:  MEDLINE    
Cerebral infarct volume is typically smaller in premenopausal females than in age-matched males after ischemic stroke, but the underlying mechanisms are poorly understood. In this study we provide evidence in mice that this gender difference only occurs when the ischemic brain is reperfused. The limited tissue salvage achieved by reperfusion in male mice is associated with increased expression of proinflammatory proteins, including cyclooxygenase-2 (Cox-2), Nox2, and vascular cell adhesion molecule-1 (VCAM-1), and infiltration of Nox2-containing T lymphocytes into the infarcted brain, whereas such changes are minimal in female mice after ischemia-reperfusion (I-R). Infarct volume after I-R was no greater at 72 h than at 24 h in either gender. Infarct development was Nox2 dependent in male but not in female mice, and Nox2 within the infarct was predominantly localized in T lymphocytes. Stroke resulted in an approximately 15-fold increase in Nox2-dependent superoxide production by circulating, but not spleen-derived, T lymphocytes in male mice, and this was approximately sevenfold greater than in female mice. These circulating immune cells may thus represent a major and previously unrecognized source of superoxide in the acutely ischemic and reperfused brain of males (and potentially in postmenopausal females). Our findings provide novel insights into mechanisms that could be therapeutically targeted in acute ischemic stroke patients who receive thrombolysis therapy to induce cerebral reperfusion.
Vanessa H Brait; Katherine A Jackman; Anna K Walduck; Stavros Selemidis; Henry Diep; Anja E Mast; Elizabeth Guida; Brad R S Broughton; Grant R Drummond; Christopher G Sobey
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-10
Journal Detail:
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:
Created Date:  2010-07-02     Completed Date:  2010-07-19     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1306-17     Citation Subset:  IM    
Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia.
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MeSH Terms
Cerebral Infarction / metabolism,  pathology*
Cerebrovascular Circulation / physiology
Cyclooxygenase 2 / metabolism
Infarction, Middle Cerebral Artery
Membrane Glycoproteins / genetics,  metabolism*
Mice, Knockout
NADPH Oxidase / genetics,  metabolism*
Random Allocation
Regional Blood Flow
Reperfusion Injury / metabolism,  pathology
Sex Factors
Stroke / metabolism,  pathology*
Superoxides / metabolism*
T-Lymphocytes / metabolism*
Vascular Cell Adhesion Molecule-1 / metabolism
Reg. No./Substance:
0/Membrane Glycoproteins; 0/Vascular Cell Adhesion Molecule-1; 11062-77-4/Superoxides; EC 1.14.99.-/Ptgs2 protein, mouse; EC 2; EC protein, mouse; EC Oxidase

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