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.