title: Effects of edaravone, a free radical scavenger, on serum levels of inflammatory biomarkers in acute brain infarction.
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.
authors.affiliation: Department of Neurology, St. Marianna University School of Medicine.
authors.forename: Kenji
authors.initials: K
authors.lastname: Isahaya
authors.forename: Koji
authors.initials: K
authors.lastname: Yamada
authors.forename: Masato
authors.initials: M
authors.lastname: Yamatoku
authors.forename: Kenzo
authors.initials: K
authors.lastname: Sakurai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takaishi
authors.forename: Bunta
authors.initials: B
authors.lastname: Kato
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Hirayama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hasegawa
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D020520:Brain Infarction / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D016009:Chi-Square Distribution; D000077553:Edaravone; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007262:Infusions, Intravenous; D007378:Interleukins / Q000097:blood; D007564:Japan; D016014:Linear Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D016166:Free Radical Scavengers; D018836:Inflammation Mediators; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077553:Edaravone; D000983:Antipyrine