title: A free radical scavenger edaravone suppresses systemic inflammatory responses in a rat transient focal ischemia model.
abstract: A free radical scavenger edaravone is clinically used in Japan for acute stroke, and several basic researches have carefully examined the mechanisms of edaravone's protective effects. However, its actions on pro-inflammatory responses under stroke are still understudied. In this study, we subjected adult male Sprague-Dawley rats to 90-min middle cerebral artery (MCA) occlusion followed by reperfusion. Edaravone was treated twice via tail vein; after MCA occlusion and after reperfusion. As expected, edaravone-treated group showed less infarct volume and edema formation compared with control group at 24-h after an ischemic onset. Furthermore, edaravone reduced the levels of plasma interleukin (IL)-1β and matrix metalloproteinase-9 at 3-h after ischemic onset. Several molecules besides IL-1β and MMP-9 are involved in inflammatory responses under stroke conditions. Therefore, we also examined whether edaravone treatment could decrease a wide range of pro-inflammatory cytokines/chemokines by testing rat plasma samples with a rat cytokine array. MCAO rats showed elevations in plasma levels of CINC-1, Fractalkine, IL-1α, IL-1ra, IL-6, IL-10, IP-10, MIG, MIP-1α, and MIP-3α, and all these increases were reduced by edaravone treatment. These data suggest that free radical scavengers may reduce systemic inflammatory responses under acute stroke conditions, and therefore, oxidative stress can be still a viable target for acute stroke therapy.
authors: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, USA.
authors: Norio
authors: N
authors: Fujiwara
authors: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, USA.
authors: Angel T
authors: AT
authors: Som
authors: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, USA.
authors: Loc-Duyen D
authors: LD
authors: Pham
authors: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, USA.
authors: Brian J
authors: BJ
authors: Lee
authors: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, USA.
authors: Emiri T
authors: ET
authors: Mandeville
authors: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, USA. Electronic address: lo@helix.mgh.harvard.edu.
authors: Eng H
authors: EH
authors: Lo
authors: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, USA. Electronic address: karai@partners.org.
authors: Ken
authors: K
authors: Arai
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001929:Brain Edema / Q000188:drug therapy; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D016207:Cytokines / Q000097:blood*; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D053583:Interleukin-1beta / Q000097:blood; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D020780:Matrix Metalloproteinase 9; D000077553:Edaravone; D000983:Antipyrine
keywords: Edaravone; Middle cerebral artery occlusion; Oxidative stress; Pro-inflammatory cytokine; Protein array; Stroke