Neuroprotective Effects of Dizocilpine (MK-801) Via Mediation of Nitric Oxide Synthase on Hypoxic-ischemic Brain Injury in Neonatal Rats / 대한주산의학회잡지

ABSTRACT

PURPOSE: Current studies have demonstrated the neuroprotective effects of dizocilpine (MK-801) in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma and excitotoxicity, but limited data are available for those during the neonatal periods. Here we investigated whether dizocilpine can protect the developing rat brain from HI injury via mediation of nitric oxide synthase. METHODS: In an in vivo model, left carotid artery ligation was done in 7-day-old Sprague-Dawley (SD) rat pups. The animals were divided into three groups; normoxia, hypoxia with operation (HO), and HO treated with dizocilpine at a dose of 10 mg/kg. Hypoxia was made by exposure to a 2 hours period of hypoxic incubator (92% N2, 8% O2). In an in vitro model, embryonic cortical neuronal cell culture of SD rats at 18-day gestation was done. The cultured cells were divided into three groups normoxia, hypoxia, and hypoxia treated with dizocilpine. The N group was prepared in 5% CO2 incubators and the other groups were placed in 1% O2 incubators (94% N2, 5% CO2) for 16 hours. RESULTS: Dizocilpin treatment significantly reduced the size of brain infarct in the neonatal rat model of HI. Both in the animal and in vitro experiments, expression of iNOS and eNOS were lower in the hypoxia group than in the normoxia group. Meanwhile, the nNOS expression was greater in the hypoxia group. Dizocilpine treatment attenuated these aberrant expressions of NOSs following hypoxic injury. CONCLUSION: Dizocilpine has neuroprotective property over perinatal HI brain injury via mediation of nitric oxide synthase.