Effects of Edaravone, a Free Radical Scavenger, on Serum Levels of Inflammatory Biomarkers in Acute Brain Infarction
The potent free radical scavenger edavarone is widely used in Japan to treat acute ischemic stroke within 24 hours after onset. Recent experimental studies have shown that edavarone alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute brain...
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creator | Isahaya, Kenji, MD Yamada, Koji, MD, PhD Yamatoku, Masato, MD Sakurai, Kenzo, MD Takaishi, Satoshi, MD, PhD Kato, Bunta, MD, PhD Hirayama, Toshikazu, MD, PhD Hasegawa, Yasuhiro, MD, PhD |
description | The potent free radical scavenger edavarone is widely used in Japan to treat acute ischemic stroke within 24 hours after onset. Recent experimental studies have shown that edavarone alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute brain ischemia. We investigated the effects of edaravone on circulating inflammatory biomarkers in patients with ischemic stroke. Patients with acute ischemic stroke admitted 12-36 hours after onset of symptoms were prospectively enrolled. Intravenous edaravone at 60 mg/day for 14 days was administered to patients admitted 12-24 hours after symptom onset (edaravone group; n = 29). Patients admitted 24-36 hours after onset served as controls (control group; n = 34). Venous blood samples were obtained on admission and at 48 hours, 7 days, and 14 days after symptom onset. Serum concentrations of high-sensitivity C-reactive protein, interleukin (IL)-6, IL-10, IL-18, tumor necrosis factor α, matrix metalloproteinase (MMP)-2, and MMP-9 were measured. General linear models were used to compare changes in concentrations of these biomarkers over time between the groups. In the control group, the mean MMP-9 concentration increased gradually from 3.857 ± 1.880 ng/mL to 4.538 ± 1.966 ng/mL over the 14-day period ( P = .027, one-way repeated-measures analysis of variance [ANOVA]), but the edavarone group demonstrated no such increase ( P = .564). A significant group–time interaction was demonstrated only for MMP-9 ( P = .029, two-way repeated-measures ANOVA), and no significant differences in other biomarkers were seen between groups. Our data indicate that edaravone suppresses serum MMP-9 level in patients with acute ischemic stroke. Further studies with a larger sample size are needed to explore the relationship between circulating MMP-9 level and the protective effect of edaravone. |
doi_str_mv | 10.1016/j.jstrokecerebrovasdis.2010.05.009 |
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Recent experimental studies have shown that edavarone alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute brain ischemia. We investigated the effects of edaravone on circulating inflammatory biomarkers in patients with ischemic stroke. Patients with acute ischemic stroke admitted 12-36 hours after onset of symptoms were prospectively enrolled. Intravenous edaravone at 60 mg/day for 14 days was administered to patients admitted 12-24 hours after symptom onset (edaravone group; n = 29). Patients admitted 24-36 hours after onset served as controls (control group; n = 34). Venous blood samples were obtained on admission and at 48 hours, 7 days, and 14 days after symptom onset. Serum concentrations of high-sensitivity C-reactive protein, interleukin (IL)-6, IL-10, IL-18, tumor necrosis factor α, matrix metalloproteinase (MMP)-2, and MMP-9 were measured. General linear models were used to compare changes in concentrations of these biomarkers over time between the groups. In the control group, the mean MMP-9 concentration increased gradually from 3.857 ± 1.880 ng/mL to 4.538 ± 1.966 ng/mL over the 14-day period ( P = .027, one-way repeated-measures analysis of variance [ANOVA]), but the edavarone group demonstrated no such increase ( P = .564). A significant group–time interaction was demonstrated only for MMP-9 ( P = .029, two-way repeated-measures ANOVA), and no significant differences in other biomarkers were seen between groups. Our data indicate that edaravone suppresses serum MMP-9 level in patients with acute ischemic stroke. Further studies with a larger sample size are needed to explore the relationship between circulating MMP-9 level and the protective effect of edaravone.</description><identifier>ISSN: 1052-3057</identifier><identifier>EISSN: 1532-8511</identifier><identifier>DOI: 10.1016/j.jstrokecerebrovasdis.2010.05.009</identifier><identifier>PMID: 21215657</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acute Disease ; Aged ; Aged, 80 and over ; Analysis of Variance ; Antipyrine - administration & dosage ; Antipyrine - analogs & derivatives ; Antipyrine - therapeutic use ; biomarker ; Biomarkers - blood ; Brain infarction ; Brain Infarction - blood ; Brain Infarction - drug therapy ; Brain Infarction - immunology ; C-Reactive Protein - metabolism ; Cardiovascular ; Chi-Square Distribution ; Female ; Free Radical Scavengers - administration & dosage ; Free Radical Scavengers - therapeutic use ; Humans ; inflammation ; Inflammation Mediators - blood ; Infusions, Intravenous ; interleukin ; Interleukins - blood ; Japan ; Linear Models ; Male ; Matrix Metalloproteinase 2 - blood ; Matrix Metalloproteinase 9 - blood ; metalloproteinase ; Middle Aged ; Neurology ; Prospective Studies ; Time Factors ; Treatment Outcome ; tumor necrosis factor α ; Tumor Necrosis Factor-alpha - blood</subject><ispartof>Journal of stroke and cerebrovascular diseases, 2012-02, Vol.21 (2), p.102-107</ispartof><rights>National Stroke Association</rights><rights>2012 National Stroke Association</rights><rights>Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c524t-bb47bbd13a3c15006e0db61ae11eccb2b9f3fac0039b69d7da6fbc8a501df3ff3</citedby><cites>FETCH-LOGICAL-c524t-bb47bbd13a3c15006e0db61ae11eccb2b9f3fac0039b69d7da6fbc8a501df3ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S105230571000128X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21215657$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Isahaya, Kenji, MD</creatorcontrib><creatorcontrib>Yamada, Koji, MD, PhD</creatorcontrib><creatorcontrib>Yamatoku, Masato, MD</creatorcontrib><creatorcontrib>Sakurai, Kenzo, MD</creatorcontrib><creatorcontrib>Takaishi, Satoshi, MD, PhD</creatorcontrib><creatorcontrib>Kato, Bunta, MD, PhD</creatorcontrib><creatorcontrib>Hirayama, Toshikazu, MD, PhD</creatorcontrib><creatorcontrib>Hasegawa, Yasuhiro, MD, PhD</creatorcontrib><title>Effects of Edaravone, a Free Radical Scavenger, on Serum Levels of Inflammatory Biomarkers in Acute Brain Infarction</title><title>Journal of stroke and cerebrovascular diseases</title><addtitle>J Stroke Cerebrovasc Dis</addtitle><description>The potent free radical scavenger edavarone is widely used in Japan to treat acute ischemic stroke within 24 hours after onset. Recent experimental studies have shown that edavarone alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute brain ischemia. We investigated the effects of edaravone on circulating inflammatory biomarkers in patients with ischemic stroke. Patients with acute ischemic stroke admitted 12-36 hours after onset of symptoms were prospectively enrolled. Intravenous edaravone at 60 mg/day for 14 days was administered to patients admitted 12-24 hours after symptom onset (edaravone group; n = 29). Patients admitted 24-36 hours after onset served as controls (control group; n = 34). Venous blood samples were obtained on admission and at 48 hours, 7 days, and 14 days after symptom onset. Serum concentrations of high-sensitivity C-reactive protein, interleukin (IL)-6, IL-10, IL-18, tumor necrosis factor α, matrix metalloproteinase (MMP)-2, and MMP-9 were measured. General linear models were used to compare changes in concentrations of these biomarkers over time between the groups. In the control group, the mean MMP-9 concentration increased gradually from 3.857 ± 1.880 ng/mL to 4.538 ± 1.966 ng/mL over the 14-day period ( P = .027, one-way repeated-measures analysis of variance [ANOVA]), but the edavarone group demonstrated no such increase ( P = .564). A significant group–time interaction was demonstrated only for MMP-9 ( P = .029, two-way repeated-measures ANOVA), and no significant differences in other biomarkers were seen between groups. Our data indicate that edaravone suppresses serum MMP-9 level in patients with acute ischemic stroke. Further studies with a larger sample size are needed to explore the relationship between circulating MMP-9 level and the protective effect of edaravone.</description><subject>Acute Disease</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis of Variance</subject><subject>Antipyrine - administration & dosage</subject><subject>Antipyrine - analogs & derivatives</subject><subject>Antipyrine - therapeutic use</subject><subject>biomarker</subject><subject>Biomarkers - blood</subject><subject>Brain infarction</subject><subject>Brain Infarction - blood</subject><subject>Brain Infarction - drug therapy</subject><subject>Brain Infarction - immunology</subject><subject>C-Reactive Protein - metabolism</subject><subject>Cardiovascular</subject><subject>Chi-Square Distribution</subject><subject>Female</subject><subject>Free Radical Scavengers - administration & dosage</subject><subject>Free Radical Scavengers - therapeutic use</subject><subject>Humans</subject><subject>inflammation</subject><subject>Inflammation Mediators - blood</subject><subject>Infusions, Intravenous</subject><subject>interleukin</subject><subject>Interleukins - blood</subject><subject>Japan</subject><subject>Linear Models</subject><subject>Male</subject><subject>Matrix Metalloproteinase 2 - blood</subject><subject>Matrix Metalloproteinase 9 - blood</subject><subject>metalloproteinase</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Prospective Studies</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>tumor necrosis factor α</subject><subject>Tumor Necrosis Factor-alpha - blood</subject><issn>1052-3057</issn><issn>1532-8511</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkl1rFDEUhgdRbK3-BcmdIJ01J9PM7NwI3bKthQXBVfAu5ONEMjuT1GRmYP-9Gbf1QrzxKgfy5D3kOaco3gNdAYX6Q7fq0hjDATVGVDHMMhmXVoxmgPIVpe2z4hx4xco1B3iea8pZWVHenBWvUuooBeBr_rI4Y8CA17w5L8attajHRIIlWyOjnIPHSyLJbUQkX6RxWvZkr-WM_gfGSxI82WOcBrLDGfvf7-697eUwyDHEI9m4MMh4wJiI8-RaTyOSTZS5zpiMenTBvy5eWNknfPN4XhTfbrdfbz6Vu8939zfXu1JzdjWWSl01ShmoZKWBU1ojNaoGiQCotWKqtZWVmtKqVXVrGiNrq_Racgom39jqonh3yn2I4eeEaRSDSxr7XnoMUxItrNsKmpplcnMidQwpRbTiIbr8j6MAKhb5ohP_ki8W-YJykeXnkLeP7SY1oPkT8WQ7A7sTkMXh7DCKpB16jcbFPARhgvu_fh__itO988vADnjE1IUp-qxXgEhMULFf1mHZBqB5E9j6e_ULsi-67A</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Isahaya, Kenji, MD</creator><creator>Yamada, Koji, MD, PhD</creator><creator>Yamatoku, Masato, MD</creator><creator>Sakurai, Kenzo, MD</creator><creator>Takaishi, Satoshi, MD, PhD</creator><creator>Kato, Bunta, MD, PhD</creator><creator>Hirayama, Toshikazu, MD, PhD</creator><creator>Hasegawa, Yasuhiro, MD, PhD</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20120201</creationdate><title>Effects of Edaravone, a Free Radical Scavenger, on Serum Levels of Inflammatory Biomarkers in Acute Brain Infarction</title><author>Isahaya, Kenji, MD ; Yamada, Koji, MD, PhD ; Yamatoku, Masato, MD ; Sakurai, Kenzo, MD ; Takaishi, Satoshi, MD, PhD ; Kato, Bunta, MD, PhD ; Hirayama, Toshikazu, MD, PhD ; Hasegawa, Yasuhiro, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c524t-bb47bbd13a3c15006e0db61ae11eccb2b9f3fac0039b69d7da6fbc8a501df3ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acute Disease</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis of Variance</topic><topic>Antipyrine - administration & dosage</topic><topic>Antipyrine - analogs & derivatives</topic><topic>Antipyrine - therapeutic use</topic><topic>biomarker</topic><topic>Biomarkers - blood</topic><topic>Brain infarction</topic><topic>Brain Infarction - blood</topic><topic>Brain Infarction - drug therapy</topic><topic>Brain Infarction - immunology</topic><topic>C-Reactive Protein - metabolism</topic><topic>Cardiovascular</topic><topic>Chi-Square Distribution</topic><topic>Female</topic><topic>Free Radical Scavengers - administration & dosage</topic><topic>Free Radical Scavengers - therapeutic use</topic><topic>Humans</topic><topic>inflammation</topic><topic>Inflammation Mediators - blood</topic><topic>Infusions, Intravenous</topic><topic>interleukin</topic><topic>Interleukins - blood</topic><topic>Japan</topic><topic>Linear Models</topic><topic>Male</topic><topic>Matrix Metalloproteinase 2 - blood</topic><topic>Matrix Metalloproteinase 9 - blood</topic><topic>metalloproteinase</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Prospective Studies</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>tumor necrosis factor α</topic><topic>Tumor Necrosis Factor-alpha - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Isahaya, Kenji, MD</creatorcontrib><creatorcontrib>Yamada, Koji, MD, PhD</creatorcontrib><creatorcontrib>Yamatoku, Masato, MD</creatorcontrib><creatorcontrib>Sakurai, Kenzo, MD</creatorcontrib><creatorcontrib>Takaishi, Satoshi, MD, PhD</creatorcontrib><creatorcontrib>Kato, Bunta, MD, PhD</creatorcontrib><creatorcontrib>Hirayama, Toshikazu, MD, PhD</creatorcontrib><creatorcontrib>Hasegawa, Yasuhiro, MD, PhD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of stroke and cerebrovascular diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Isahaya, Kenji, MD</au><au>Yamada, Koji, MD, PhD</au><au>Yamatoku, Masato, MD</au><au>Sakurai, Kenzo, MD</au><au>Takaishi, Satoshi, MD, PhD</au><au>Kato, Bunta, MD, PhD</au><au>Hirayama, Toshikazu, MD, PhD</au><au>Hasegawa, Yasuhiro, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Edaravone, a Free Radical Scavenger, on Serum Levels of Inflammatory Biomarkers in Acute Brain Infarction</atitle><jtitle>Journal of stroke and cerebrovascular diseases</jtitle><addtitle>J Stroke Cerebrovasc Dis</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>21</volume><issue>2</issue><spage>102</spage><epage>107</epage><pages>102-107</pages><issn>1052-3057</issn><eissn>1532-8511</eissn><abstract>The potent free radical scavenger edavarone is widely used in Japan to treat acute ischemic stroke within 24 hours after onset. Recent experimental studies have shown that edavarone alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute brain ischemia. We investigated the effects of edaravone on circulating inflammatory biomarkers in patients with ischemic stroke. Patients with acute ischemic stroke admitted 12-36 hours after onset of symptoms were prospectively enrolled. Intravenous edaravone at 60 mg/day for 14 days was administered to patients admitted 12-24 hours after symptom onset (edaravone group; n = 29). Patients admitted 24-36 hours after onset served as controls (control group; n = 34). Venous blood samples were obtained on admission and at 48 hours, 7 days, and 14 days after symptom onset. Serum concentrations of high-sensitivity C-reactive protein, interleukin (IL)-6, IL-10, IL-18, tumor necrosis factor α, matrix metalloproteinase (MMP)-2, and MMP-9 were measured. General linear models were used to compare changes in concentrations of these biomarkers over time between the groups. In the control group, the mean MMP-9 concentration increased gradually from 3.857 ± 1.880 ng/mL to 4.538 ± 1.966 ng/mL over the 14-day period ( P = .027, one-way repeated-measures analysis of variance [ANOVA]), but the edavarone group demonstrated no such increase ( P = .564). A significant group–time interaction was demonstrated only for MMP-9 ( P = .029, two-way repeated-measures ANOVA), and no significant differences in other biomarkers were seen between groups. Our data indicate that edaravone suppresses serum MMP-9 level in patients with acute ischemic stroke. Further studies with a larger sample size are needed to explore the relationship between circulating MMP-9 level and the protective effect of edaravone.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21215657</pmid><doi>10.1016/j.jstrokecerebrovasdis.2010.05.009</doi><tpages>6</tpages></addata></record> |
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subjects | Acute Disease Aged Aged, 80 and over Analysis of Variance Antipyrine - administration & dosage Antipyrine - analogs & derivatives Antipyrine - therapeutic use biomarker Biomarkers - blood Brain infarction Brain Infarction - blood Brain Infarction - drug therapy Brain Infarction - immunology C-Reactive Protein - metabolism Cardiovascular Chi-Square Distribution Female Free Radical Scavengers - administration & dosage Free Radical Scavengers - therapeutic use Humans inflammation Inflammation Mediators - blood Infusions, Intravenous interleukin Interleukins - blood Japan Linear Models Male Matrix Metalloproteinase 2 - blood Matrix Metalloproteinase 9 - blood metalloproteinase Middle Aged Neurology Prospective Studies Time Factors Treatment Outcome tumor necrosis factor α Tumor Necrosis Factor-alpha - blood |
title | Effects of Edaravone, a Free Radical Scavenger, on Serum Levels of Inflammatory Biomarkers in Acute Brain Infarction |
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