Abstract
Objective To investigate the effects of endaravane on hypoxia-ischemia (HI)-induced brain injury in neonatal piglets. Methods Male piglets 3-7 days old weighing 2.0-3.0 kg were used in this study. Group Ⅰ 10 piglets were randomly collected as sham operation without HI. Twenty piglets with HI were randomly divided into 2 groups (n = 10 each) : group Ⅱ HI and group Ⅲ HI + endaravone. The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg, tracheostomized and mechanically ventilated with 30% O2. Right femoral artery and vein were cannulated. MAP, HR, PET CO2, blood gases and glucose and rectal temperature were monitored. After 15 min stabilization cardiac arrest was induced by inhalation of hypoxic air (O2 10%) for 40 min followed by inhalation of 21% O2 for 5 min. The tracheal tube was then occluded for 7 min. Cardio-pulmonary resuscitation (CPR) was then started until recovery of spontaneous circulation (ROSC). CPR > 3 min was considered a failure. A bolus of endaravone 3 mg/kg was given iv over an hour at 30 min after CPR,followed by continuous infusion at 1.5 mg·kg-1·h-1 for 5.5 h in group Ⅲ , while in group Ⅱ vehicle was given instead of endaravone. The neurological function of the animals was evaluated at 48, 72 and 96 h after ROSC and scored (0-154, 0 = normal, 154 = severest dysfunction). The animals were killed at 96 h after ROSC. The brains were removed for microscopic examination of striatum and cortex and determination of 8-hydroxy-2'-deoxyguanine (8-OHdG/OHG) expression in putamen by immuno-histochemistry. Results The neurological function scores were significantly higher at 48 h after ROSC and the number of viable neurons in striatum and sensory cortex were significantly lower and the expression of 8-OHdG/OHG in putamen was significantly higher in group Ⅱ than in group Ⅲ . Conclusion The antioxidant endaravone given after CPR can attenuate Hl-induced brain injury by inhibiting oxidative damage to DNA and RNA. Key words: Antipyrine; Hypoxia-ischemia, Brain; Infant, newborn
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