Edaravone inhibits lipid peroxidation in neonatal hypoxic-ischemic rats: an in vivo microdialysis study

Neurosci Lett. 2007 Feb 27;414(1):5-9. doi: 10.1016/j.neulet.2006.10.024. Epub 2007 Feb 5.


The occurrence of hypoxia-ischemia (HI) during early fetal or neonatal stages of an individual leads to the damaging of immature neurons resulting in behavioral and psychological dysfunctions. Free radical-mediated lipid peroxidation is the main cause of neurotoxicity including neonatal brain damage. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a novel anti-oxidant agent and the drug of choice in the treatment of acute ischemic brain disorders in adult patient. The purpose of this study is to determine the direct effects of edaravone in inhibiting the lipid peroxidation production in the neonatal rat brains during hypoxic-ischemic insult by electron paramagnetic resonance (EPR) spectoroscopy and in vivo brain microdialysis. Seven-day-old Wistar rats were subjected to left common carotid artery ligation and a probe was inserted in the rat hippocampus. Edaravone (5, 50, or 100 microM) or saline was perfused with a spin trap agent (alpha-(4-pyridyl-N-oxide)-N-tert-butylnitrone; POBN) before, during and after hypoxia (1h of 8% O2 exposure) and then analyzed by EPR. Edaravone (100 microM) did not show any EPR evidence of POBN adduct formation during and after hypoxic-ischemic insult. However, the EPR signal increased, but not significantly during the hypoxic period in the hypoxic and edaravone 50 microM-treated groups compared to control. Edaravone at 5 microM significantly increased the EPR signals compared to control. This study shows that edaravone directly and dose-dependently inhibited the formation of lipid free radicals produced during hypoxic-ischemic insult in the neonatal rat brain. These results suggest that edaravone is able to attenuate neuronal damage in the rat neonatal brain by inhibiting the formation of lipid radicals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antipyrine / analogs & derivatives*
  • Antipyrine / pharmacology
  • Dose-Response Relationship, Drug
  • Edaravone
  • Electron Spin Resonance Spectroscopy
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Free Radical Scavengers / pharmacology
  • Free Radicals / antagonists & inhibitors
  • Free Radicals / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / metabolism
  • Hypoxia-Ischemia, Brain / physiopathology
  • Lipid Peroxidation / drug effects*
  • Lipid Peroxidation / physiology
  • Microdialysis
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / physiopathology
  • Nerve Degeneration / prevention & control
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Pyridines
  • Rats
  • Rats, Wistar
  • Treatment Outcome


  • (pyridyl-4-N-oxide)-N-tert-butylnitrone
  • Free Radical Scavengers
  • Free Radicals
  • Pyridines
  • Edaravone
  • Antipyrine