title: Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury: Implications for Perioperative Neuroprotection.
abstract: OBJECTIVE
  Hypoperfusion-induced thrombosis is an important mechanism for postsurgery stroke and cognitive decline, but there are no perioperative neuroprotectants to date. This study investigated whether prophylactic application of Edaravone, a free radical scavenger already used in treating ischemic stroke in Japan, can prevent infarct and cognitive deficits in a murine model of transient cerebral hypoxia-ischemia.
  
  
  METHODS
  Adult male C57BL/6 mice were subjected to transient hypoxic-ischemic (tHI) insult that consists of 30-minute occlusion of the unilateral common carotid artery and exposure to 7.5% oxygen. Edaravone or saline was prophylactically applied to compare their effects on cortical oxygen saturation, blood flow, coagulation, oxidative stress, metabolites, and learning-memory using methods that include photoacoustic imaging, laser speckle contrast imaging, solid-state NMR, and Morris water maze. The effects on infarct size by Edaravone application at different time points after tHI were also compared.
  
  
  RESULTS
  Prophylactic administration of Edaravone (4.5 mg/kg×2, IP, 1 hour before and 1 hour after tHI) improved vascular reperfusion, oxygen saturation, and the maintenance of brain metabolites, reducing oxidative stress, thrombosis, white-matter injury, and learning impairment after tHI insult. Delayed Edaravone treatment after 3 h post-tHI became unable to reduce infarct size.
  
  
  CONCLUSIONS
  Acute application of Edaravone may be a useful strategy to prevent postsurgery stroke and cognitive impairment, especially in patients with severe carotid stenosis.
authors.affiliation: From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.).
authors.forename: Yu-Yo
authors.initials: YY
authors.lastname: Sun
authors.affiliation: From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.).
authors.forename: Yikun
authors.initials: Y
authors.lastname: Li
authors.affiliation: From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.).
authors.forename: Bushra
authors.initials: B
authors.lastname: Wali
authors.affiliation: From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.).
authors.forename: Yuancheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.).
authors.forename: Jolly
authors.initials: J
authors.lastname: Lee
authors.affiliation: From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.).
authors.forename: Andrew
authors.initials: A
authors.lastname: Heinmiller
authors.affiliation: From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.).
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.affiliation: From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.).
authors.forename: Donald G
authors.initials: DG
authors.lastname: Stein
authors.affiliation: From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.).
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
authors.affiliation: From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.).
authors.forename: Iqbal
authors.initials: I
authors.lastname: Sayeed
authors.affiliation: From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.). alex.kuan@emory.edu.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Kuan
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D019990:Perioperative Care / Q000379:methods; D011897:Random Allocation
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D000077553:Edaravone; D000983:Antipyrine
keywords: MCI-186; antioxidants; stroke; thrombosis