title: Neuroprotection of edaravone on hypoxic-ischemic brain injury in neonatal rats.
abstract: Edaravone has an inhibitory effect on lipid peroxidation by scavenging free radicals and prevents vascular endothelial cell injury. We examined whether edaravone was effective on hypoxic-ischemic (HI) brain injury in immature brain or not using the Rice-Vannucci model. The initial dose, 3 mg/kg (0.05 ml) of edaravone, was injected intraperitoneally just before hypoxic exposure. Subsequently, the same dose was injected every 12 h until the animals were killed. Controls received saline injection as the same protocol. Macroscopic evaluation of brain injury revealed that the neuroprotective effect of edaravone on HI brain after 48 h post HI. TUNEL showed that edaravone injection decreased neurodegeneration. Quantitative analysis of cell death using H&E-stained 2.5 microm sections showed that there was a trend for both necrotic and apoptotic cells to decrease in edaravone injection group. Edaravone injection inhibited the release of cytochrome c from mitochondria to cytosol and caspase-3 activation in cortex and hippocampus between 24 and 168 h post HI. Our results suggest that edaravone is protective after HI insult in the immature brain by decreasing both apoptosis and necrosis and also by inhibiting mitochondrial injury.
authors.affiliation: Department of Pediatrics, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yasuoka
authors.forename: Wako
authors.initials: W
authors.lastname: Nakajima
authors.forename: Akira
authors.initials: A
authors.lastname: Ishida
authors.forename: Goro
authors.initials: G
authors.lastname: Takada
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D000077553:Edaravone; D020925:Hypoxia-Ischemia, Brain / Q000517:prevention & control*; D020287:In Situ Nick-End Labeling / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D000077553:Edaravone; D000983:Antipyrine