Neuroprotective Effects of Amantadine on the Hypoxic-ischemic Brain Inj ury of Neonatal Rats / 华中科技大学学报(医学版)

ABSTRACT

Objective To examine the neuroprotective effects of amantadine(AMA),a non-competitive NMDA receptor an-tagonist,on the hypoxic-ischemic(HI)brain injury of neonatal rats and the possible mechanisms.Methods Hypoxic-ischemic encephalopathy(HIE)models were established in seven-day-old male and female Sprague-Dawley rats by ligating the right ce-phalic artery and then inhaling 8% oxygen for 2 h.All the rats were divided into 3 groupscontrol group(n=15),HIE group(n=15),and AMA group(n=45).Animals in AMA group were intranasally treated with AMA at 50 mg/kg 30 min before and 15 min after ligation and 30 min before inhalation(15 rats each used at the three time points).The right-to-left hemispheric weight ratio was calculated 7 days after the HI brain injury.The right hippocampus tissues of rats(n=45)were harvested 24 h after the HI brain injury and the concentrations of IL-1βand IL-6 were detected by ELISA.The outcomes of behavior tests(in-volving 45 rats)including Barnes maze test,motor coordination test and fear conditioning test,were evaluated 30 days after the HI brain injury.Results Intranasal AMA significantly increased the right-to-left hemispheric weight ratio,lowered the concen-trations of IL-1βand IL-6 in the right hippocampus of rats and promoted the behavior functions 15 min after ligation(P<0.05) . Conclusion Intranasal AMA can provide neuroprotection partially by reducing the hippocampal inflammation in the neonatal rats with HI brain injury.