Foundation Item: Supported by national science foundation of China(30470598)Neuroprotective Effects of Edaravone on Neonatal Mice with Hypoxia-Ischemia Brain Damage / 实用儿科临床杂志

ABSTRACT

ObjectiveTo evaluate the neuroprotective effect and possible mechanisms of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) in neonatal Harlequin (Hq) mutant mice brain after hypoxia-ischemia brain injury(HIBD) insult.MethodsThe nine-day-old male Hq mutant mouse pups were assigned randomly either edaravone (n=16) and vehicle (n=17) treatment group. The Hq mice were subjected to left common carotid artery occlusion combined with inhalation 100 mL/L oxygen for 45 minutes. The mice were injected intraperitoneally either with edaravone (10 mg/kg) or equivalent volume of saline immediately after artery occlusion and after hypoxia. Nitrotyrosine and lipid peroxidation formation were evaluated at 3 h and 24 h after hypoxia-ischemia(HI) by using immunohistochemistry staining. Nitrotyrosine formation and caspases activation were evaluated either by immunoblotting or fluorogenic activity measurement at 24 h after HI. Brain injury was evaluated at 72 h by neuropathological score and calculating the infarct volume.ResultsBrain injury encompassed cortex, hippocampus, striatum and thalamus. Edaravone treatment reduced brain injury significantly in all the brain regions. The total infarct volume was reduced 52.8% in edaravone treatment group compared with vehicle group (P<0.001). The edaravone treatment reduced nitrotyrosine formation as well as lipid peroxidation formation significantly, but without obviously effect on caspases activation.ConclusionEdaravone affords neuroprotection after neonatal HI insult, which correlated with the reduction of free radical formation.