OXIDATIVE STRESS IN ISCHEMIC STROKE: THE DAMAGING POTENTIAL OF ACTIVATED NEUTROPHILS

2.50
Hdl Handle:
http://hdl.handle.net/10755/157304
Type:
Presentation
Title:
OXIDATIVE STRESS IN ISCHEMIC STROKE: THE DAMAGING POTENTIAL OF ACTIVATED NEUTROPHILS
Abstract:
OXIDATIVE STRESS IN ISCHEMIC STROKE: THE DAMAGING POTENTIAL OF ACTIVATED NEUTROPHILS
Conference Sponsor:Western Institute of Nursing
Conference Year:2010
Author:Morrison, Helena, RN, BS, BSN
P.I. Institution Name:The University of Arizona
Title:Doctoral Student
Contact Address:1305 N. Martin, PO Box 210203, Tucson, AZ, 85721, USA
Co-Authors:Leslie S. Ritter
PURPOSE: The purpose of this paper is to review oxidative stress during reperfusion after ischemic stroke with an emphasis on the damaging potential of the activated neutrophil.
BACKGROUND/RATIONALE The restoration of blood flow to ischemic tissue (reperfusion) is necessary to reduce injury after stroke. However, upon the return of oxygen to ischemic cells undergoing anabolic metabolism, oxygen binds to biochemical and molecular products of anaerobic metabolism resulting in the production of reactive oxygen species (ROS). ROS are produced from multiple cell types during reperfusion after ischemic stroke. Activated neutrophils are a major source of the potent ROS hydrogen peroxide (H2O2), formed when neutophil NADPH oxidase assembles in the membrane, catalyzing the reaction 2O2 + NADPH?NADP+ + 2O2- + H+. Superoxide (2O2-) then readily combines with existing hydrogen to form H2O2. During reperfusion after ischemic stroke, ROS production increases beyond the production of endogenous antioxidants. This imbalance is termed oxidative stress. Oxidative stress damages brain tissue via oxidation of lipids, proteins, and alterations of intracellular signaling pathways that change gene transcription and protein synthesis. Compared to other tissues, the brain is highly susceptible to ROS-induced oxidative stress because brain tissue contains a high concentration of lipids, a key target of ROS. Further, it is known that oxidative stress activates additional inflammatory pathways, such as the complement system. Thus, ROS acts directly and indirectly to perpetuate a toxic environment that results in increased brain tissue damage during reperfusion following ischemic stroke. Because neutrophils are chronically activated (primed) in diabetic rodents before the onset of stroke, we hypothesized that there would be exaggerated neutrophil ROS production during reperfusion after ischemic stroke.
METHODS: Flow cytometry was used to investigate the damaging potential of activated systemic neutrophils in diabetic rodent models of ischemic stroke and reperfusion. Hydrogen peroxide, a product of the neutrophil NADPH oxidase mediated reaction, oxidizes to the fluorescent chemical dichlorofluorescein (DCF). DCF fluorescence can then be detected with flow cytometry techniques. In this study, neutrophil ROS production was measured before and immediately after reperfusion following 2 hours of ischemic stroke in a rodent model of type 2 diabetes vs. lean controls.
RESULTS/IMPLICATIONS: We found a significant increase in neutrophil ROS production during early reperfusion after stroke in diabetic animals vs. lean controls. This confirms that the DCF-flow cytometry method is a sensitive measure of neutrophil ROS production. We are currently investigating the impact of a natural product on reducing oxidant stress in a diabetic model of ischemic stroke and reperfusion.
Repository Posting Date:
26-Oct-2011
Date of Publication:
17-Oct-2011
Sponsors:
Western Institute of Nursing

Full metadata record

DC FieldValue Language
dc.typePresentationen_GB
dc.titleOXIDATIVE STRESS IN ISCHEMIC STROKE: THE DAMAGING POTENTIAL OF ACTIVATED NEUTROPHILSen_GB
dc.identifier.urihttp://hdl.handle.net/10755/157304-
dc.description.abstract<table><tr><td colspan="2" class="item-title">OXIDATIVE STRESS IN ISCHEMIC STROKE: THE DAMAGING POTENTIAL OF ACTIVATED NEUTROPHILS</td></tr><tr class="item-sponsor"><td class="label">Conference Sponsor:</td><td class="value">Western Institute of Nursing</td></tr><tr class="item-year"><td class="label">Conference Year:</td><td class="value">2010</td></tr><tr class="item-author"><td class="label">Author:</td><td class="value">Morrison, Helena, RN, BS, BSN</td></tr><tr class="item-institute"><td class="label">P.I. Institution Name:</td><td class="value">The University of Arizona</td></tr><tr class="item-author-title"><td class="label">Title:</td><td class="value">Doctoral Student</td></tr><tr class="item-address"><td class="label">Contact Address:</td><td class="value">1305 N. Martin, PO Box 210203, Tucson, AZ, 85721, USA</td></tr><tr class="item-email"><td class="label">Email:</td><td class="value">hmorrison@nursing.arizona.edu</td></tr><tr class="item-co-authors"><td class="label">Co-Authors:</td><td class="value">Leslie S. Ritter</td></tr><tr><td colspan="2" class="item-abstract">PURPOSE: The purpose of this paper is to review oxidative stress during reperfusion after ischemic stroke with an emphasis on the damaging potential of the activated neutrophil. <br/>BACKGROUND/RATIONALE The restoration of blood flow to ischemic tissue (reperfusion) is necessary to reduce injury after stroke. However, upon the return of oxygen to ischemic cells undergoing anabolic metabolism, oxygen binds to biochemical and molecular products of anaerobic metabolism resulting in the production of reactive oxygen species (ROS). ROS are produced from multiple cell types during reperfusion after ischemic stroke. Activated neutrophils are a major source of the potent ROS hydrogen peroxide (H2O2), formed when neutophil NADPH oxidase assembles in the membrane, catalyzing the reaction 2O2 + NADPH?NADP+ + 2O2- + H+. Superoxide (2O2-) then readily combines with existing hydrogen to form H2O2. During reperfusion after ischemic stroke, ROS production increases beyond the production of endogenous antioxidants. This imbalance is termed oxidative stress. Oxidative stress damages brain tissue via oxidation of lipids, proteins, and alterations of intracellular signaling pathways that change gene transcription and protein synthesis. Compared to other tissues, the brain is highly susceptible to ROS-induced oxidative stress because brain tissue contains a high concentration of lipids, a key target of ROS. Further, it is known that oxidative stress activates additional inflammatory pathways, such as the complement system. Thus, ROS acts directly and indirectly to perpetuate a toxic environment that results in increased brain tissue damage during reperfusion following ischemic stroke. Because neutrophils are chronically activated (primed) in diabetic rodents before the onset of stroke, we hypothesized that there would be exaggerated neutrophil ROS production during reperfusion after ischemic stroke. <br/>METHODS: Flow cytometry was used to investigate the damaging potential of activated systemic neutrophils in diabetic rodent models of ischemic stroke and reperfusion. Hydrogen peroxide, a product of the neutrophil NADPH oxidase mediated reaction, oxidizes to the fluorescent chemical dichlorofluorescein (DCF). DCF fluorescence can then be detected with flow cytometry techniques. In this study, neutrophil ROS production was measured before and immediately after reperfusion following 2 hours of ischemic stroke in a rodent model of type 2 diabetes vs. lean controls. <br/>RESULTS/IMPLICATIONS: We found a significant increase in neutrophil ROS production during early reperfusion after stroke in diabetic animals vs. lean controls. This confirms that the DCF-flow cytometry method is a sensitive measure of neutrophil ROS production. We are currently investigating the impact of a natural product on reducing oxidant stress in a diabetic model of ischemic stroke and reperfusion. <br/></td></tr></table>en_GB
dc.date.available2011-10-26T19:45:05Z-
dc.date.issued2011-10-17en_GB
dc.date.accessioned2011-10-26T19:45:05Z-
dc.description.sponsorshipWestern Institute of Nursingen_GB
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