The Neuroprotective Effects of 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) Via Mediation of Nitric Oxide Synthase on Hypoxic-ischemic Brain Injury in Neonatal Rats.

Jung,  Ji Eun; Keum,  Kyung Hae; Choi,  Eun Jin; Kim,  Jin Kyung; Chung,  Hai Lee; Kim,  Woo Taek

doi:2011.18.1.59

Neonatal Med > Volume 18(1); 2011 > Article

Original Article

Journal of the Korean Society of Neonatology 2011;18(1):59-69.
DOI: https://doi.org/10.5385/jksn.2011.18.1.59 Published online May 15, 2011.

The Neuroprotective Effects of 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) Via Mediation of Nitric Oxide Synthase on Hypoxic-ischemic Brain Injury in Neonatal Rats.

Ji Eun Jung, Kyung Hae Keum, Eun Jin Choi, Jin Kyung Kim, Hai Lee Chung, Woo Taek Kim

Department of Pediatrics, School of Medicine, Catholic University of Daegu, Daegu, Korea. wootykim@cu.ac.kr

Abstract

PURPOSE
Current studies have demonstrated the neuroprotective effects of 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) in many animal models of brain injury, including hypoxic-ischemic (HI) encephlopathy, trauma and excitotoxicity, but limited data are available for those during the neonatal periods. Here we investigated whether CNQX 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 six groups; normoxia (N), hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with CNQX at a dose of 10 mg/kg (HC). Hypoxia was made by exposure to a 2 hr period in the hypoxic chamber (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 (N), hypoxia (H), and hypoxia treated with CNQX (HC). 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 hr.
RESULTS
In the in vitvo and in vivo models, the expressions of iNOS and eNOS were reduced in the hypoxia group when compared to the normoxia group, whereas they were increased in the CNQX-treated group compared to the hypoxia group. In contrast, the expression of nNOS was showed reversely.
CONCLUSION
CNQX has neuroprotective property over perinatal HI brain injury via mediation of nitric oxide synthase.

Key Words: CNQX; Nitric oxide synthase; Cerebral ischemia; Neuroprotection