Edaravone, a free radical scavenger, protects components of the neurovascular unit against oxidative stress in vitro
Abstract The concept of the neurovascular unit suggests that to be successful, stroke therapies must protect all neuronal, glial and endothelial components in brain. In this study, we tested the efficacy of the free radical scavenger edaravone in three cellular models of oxidative stress. HT22 neuro...
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Veröffentlicht in: | Brain research 2010-01, Vol.1307, p.22-27 |
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description | Abstract The concept of the neurovascular unit suggests that to be successful, stroke therapies must protect all neuronal, glial and endothelial components in brain. In this study, we tested the efficacy of the free radical scavenger edaravone in three cellular models of oxidative stress. HT22 neuronal cells were subjected to oxidative stress using the standard glutamate-induced glutathione depletion model. Primary rat astrocytes were exposed to H2 O2 . Oxidative stress was induced in human brain endothelial cells with sodium nitroprusside (SNP). Edaravone significantly reduced oxidative cell death in both HT22 neuronal cells and primary rat astrocytes in a dose-dependent manner. SNP did not kill brain endothelial cells but instead reduced their production of brain-derived neurotrophic factor (BDNF). Edaravone significantly ameliorated this response. These data suggest that free radical scavengers are effective in all cell types of the neurovascular unit, and should still be considered as a potential therapeutic approach for stroke. |
doi_str_mv | 10.1016/j.brainres.2009.10.026 |
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In this study, we tested the efficacy of the free radical scavenger edaravone in three cellular models of oxidative stress. HT22 neuronal cells were subjected to oxidative stress using the standard glutamate-induced glutathione depletion model. Primary rat astrocytes were exposed to H2 O2 . Oxidative stress was induced in human brain endothelial cells with sodium nitroprusside (SNP). Edaravone significantly reduced oxidative cell death in both HT22 neuronal cells and primary rat astrocytes in a dose-dependent manner. SNP did not kill brain endothelial cells but instead reduced their production of brain-derived neurotrophic factor (BDNF). Edaravone significantly ameliorated this response. These data suggest that free radical scavengers are effective in all cell types of the neurovascular unit, and should still be considered as a potential therapeutic approach for stroke.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2009.10.026</identifier><identifier>PMID: 19840779</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Analysis of Variance ; Animals ; Animals, Newborn ; Antipyrine - analogs & derivatives ; Antipyrine - pharmacology ; Astrocyte ; Astrocytes - drug effects ; Brain-Derived Neurotrophic Factor - metabolism ; Cell Death - drug effects ; Cerebral Cortex - cytology ; Dose-Response Relationship, Drug ; Endothelial cell ; Endothelial Cells - drug effects ; Enzyme-Linked Immunosorbent Assay - methods ; Free Radical Scavengers - pharmacology ; Glutamic Acid - toxicity ; Hippocampus - cytology ; Humans ; Hydrogen Peroxide - toxicity ; L-Lactate Dehydrogenase - metabolism ; Mice ; Neurology ; Neuron ; Neurons - drug effects ; Neurovascular unit ; Nitric Oxide Donors - pharmacology ; Nitroprusside - pharmacology ; Oxidative stress ; Oxidative Stress - drug effects ; Rats ; Rats, Sprague-Dawley ; Stroke</subject><ispartof>Brain research, 2010-01, Vol.1307, p.22-27</ispartof><rights>Elsevier B.V.</rights><rights>2009 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c591t-e27f448a20d7ac8bdba9c07596c42f2244722fc150961bacfdf6e592986603f53</citedby><cites>FETCH-LOGICAL-c591t-e27f448a20d7ac8bdba9c07596c42f2244722fc150961bacfdf6e592986603f53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.brainres.2009.10.026$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19840779$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Brian J</creatorcontrib><creatorcontrib>Egi, Yasuhiro</creatorcontrib><creatorcontrib>van Leyen, Klaus</creatorcontrib><creatorcontrib>Lo, Eng H</creatorcontrib><creatorcontrib>Arai, Ken</creatorcontrib><title>Edaravone, a free radical scavenger, protects components of the neurovascular unit against oxidative stress in vitro</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Abstract The concept of the neurovascular unit suggests that to be successful, stroke therapies must protect all neuronal, glial and endothelial components in brain. In this study, we tested the efficacy of the free radical scavenger edaravone in three cellular models of oxidative stress. HT22 neuronal cells were subjected to oxidative stress using the standard glutamate-induced glutathione depletion model. Primary rat astrocytes were exposed to H2 O2 . Oxidative stress was induced in human brain endothelial cells with sodium nitroprusside (SNP). Edaravone significantly reduced oxidative cell death in both HT22 neuronal cells and primary rat astrocytes in a dose-dependent manner. SNP did not kill brain endothelial cells but instead reduced their production of brain-derived neurotrophic factor (BDNF). Edaravone significantly ameliorated this response. These data suggest that free radical scavengers are effective in all cell types of the neurovascular unit, and should still be considered as a potential therapeutic approach for stroke.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Antipyrine - analogs & derivatives</subject><subject>Antipyrine - pharmacology</subject><subject>Astrocyte</subject><subject>Astrocytes - drug effects</subject><subject>Brain-Derived Neurotrophic Factor - metabolism</subject><subject>Cell Death - drug effects</subject><subject>Cerebral Cortex - cytology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Endothelial cell</subject><subject>Endothelial Cells - drug effects</subject><subject>Enzyme-Linked Immunosorbent Assay - methods</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Glutamic Acid - toxicity</subject><subject>Hippocampus - cytology</subject><subject>Humans</subject><subject>Hydrogen Peroxide - toxicity</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>Mice</subject><subject>Neurology</subject><subject>Neuron</subject><subject>Neurons - drug effects</subject><subject>Neurovascular unit</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Nitroprusside - pharmacology</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Stroke</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk1v1DAQtRCILoW_UPkHNNuxkzjxpQJVhSJV4gCcLccZb71k7ZXtRPTf42jL54WT7fGbN2_mDSEXDLYMmLjab4eonY-YthxAluAWuHhGNqzveCV4A8_JBgBE1UtZn5FXKe3Ls64lvCRnTPYNdJ3ckHw76qiX4PGSamojIo16dEZPNBm9oN9hvKTHGDKanKgJh2PB-nINluYHpB7nGBadzDzpSGfvMtW7oixlGr67UWe3IE25CE3Uebq4HMNr8sLqKeGbp_OcfH1_--Xmrrr_9OHjzbv7yrSS5Qp5Z5um1xzGTpt-GActDXStFKbhlvOm6Ti3hrUgBRu0saMV2EoueyGgtm19Tq5PvMd5OOBoiu6oJ3WM7qDjowraqb9_vHtQu7Ao3smuAVYIxInAxJBSRPsrl4FafVB79dMHtfqwxosPJfHiz8q_054GXwBvTwAs_S8Oo0rGoTc4ulgmrcbg_l_j-h8KMzm_WvcNHzHtwxx9ma5iKnEF6vO6DesygATO-hrqHyhRtfY</recordid><startdate>20100111</startdate><enddate>20100111</enddate><creator>Lee, Brian J</creator><creator>Egi, Yasuhiro</creator><creator>van Leyen, Klaus</creator><creator>Lo, Eng H</creator><creator>Arai, Ken</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20100111</creationdate><title>Edaravone, a free radical scavenger, protects components of the neurovascular unit against oxidative stress in vitro</title><author>Lee, Brian J ; Egi, Yasuhiro ; van Leyen, Klaus ; Lo, Eng H ; Arai, Ken</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c591t-e27f448a20d7ac8bdba9c07596c42f2244722fc150961bacfdf6e592986603f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Antipyrine - analogs & derivatives</topic><topic>Antipyrine - pharmacology</topic><topic>Astrocyte</topic><topic>Astrocytes - drug effects</topic><topic>Brain-Derived Neurotrophic Factor - metabolism</topic><topic>Cell Death - drug effects</topic><topic>Cerebral Cortex - cytology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Endothelial cell</topic><topic>Endothelial Cells - drug effects</topic><topic>Enzyme-Linked Immunosorbent Assay - methods</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>Glutamic Acid - toxicity</topic><topic>Hippocampus - cytology</topic><topic>Humans</topic><topic>Hydrogen Peroxide - toxicity</topic><topic>L-Lactate Dehydrogenase - metabolism</topic><topic>Mice</topic><topic>Neurology</topic><topic>Neuron</topic><topic>Neurons - drug effects</topic><topic>Neurovascular unit</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Nitroprusside - pharmacology</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Stroke</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Brian J</creatorcontrib><creatorcontrib>Egi, Yasuhiro</creatorcontrib><creatorcontrib>van Leyen, Klaus</creatorcontrib><creatorcontrib>Lo, Eng H</creatorcontrib><creatorcontrib>Arai, Ken</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Brian J</au><au>Egi, Yasuhiro</au><au>van Leyen, Klaus</au><au>Lo, Eng H</au><au>Arai, Ken</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Edaravone, a free radical scavenger, protects components of the neurovascular unit against oxidative stress in vitro</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2010-01-11</date><risdate>2010</risdate><volume>1307</volume><spage>22</spage><epage>27</epage><pages>22-27</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><abstract>Abstract The concept of the neurovascular unit suggests that to be successful, stroke therapies must protect all neuronal, glial and endothelial components in brain. In this study, we tested the efficacy of the free radical scavenger edaravone in three cellular models of oxidative stress. HT22 neuronal cells were subjected to oxidative stress using the standard glutamate-induced glutathione depletion model. Primary rat astrocytes were exposed to H2 O2 . Oxidative stress was induced in human brain endothelial cells with sodium nitroprusside (SNP). Edaravone significantly reduced oxidative cell death in both HT22 neuronal cells and primary rat astrocytes in a dose-dependent manner. SNP did not kill brain endothelial cells but instead reduced their production of brain-derived neurotrophic factor (BDNF). Edaravone significantly ameliorated this response. These data suggest that free radical scavengers are effective in all cell types of the neurovascular unit, and should still be considered as a potential therapeutic approach for stroke.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>19840779</pmid><doi>10.1016/j.brainres.2009.10.026</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Analysis of Variance Animals Animals, Newborn Antipyrine - analogs & derivatives Antipyrine - pharmacology Astrocyte Astrocytes - drug effects Brain-Derived Neurotrophic Factor - metabolism Cell Death - drug effects Cerebral Cortex - cytology Dose-Response Relationship, Drug Endothelial cell Endothelial Cells - drug effects Enzyme-Linked Immunosorbent Assay - methods Free Radical Scavengers - pharmacology Glutamic Acid - toxicity Hippocampus - cytology Humans Hydrogen Peroxide - toxicity L-Lactate Dehydrogenase - metabolism Mice Neurology Neuron Neurons - drug effects Neurovascular unit Nitric Oxide Donors - pharmacology Nitroprusside - pharmacology Oxidative stress Oxidative Stress - drug effects Rats Rats, Sprague-Dawley Stroke |
title | Edaravone, a free radical scavenger, protects components of the neurovascular unit against oxidative stress in vitro |
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