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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Veröffentlicht in:Journal of stroke and cerebrovascular diseases 2012-02, Vol.21 (2), p.102-107
Hauptverfasser: 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
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container_end_page 107
container_issue 2
container_start_page 102
container_title Journal of stroke and cerebrovascular diseases
container_volume 21
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. 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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. 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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.</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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