Neuroprotective Effect of Dizocilpine (MK-801) via Anti-apoptosis on Hypoxic-ischemic Brain Injury in Neonatal Rats
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Purpose: Current studies have demonstrated the neuroprotective effects of dizocilpine (MK-801) 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 dizocilpine can protect the developing rat brain from HI injury via anti-apoptosis. Methods: In an in vitro model, embryonic cortical neuronal cell culture of Sprague-Dawley (SD) rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with dizocilpine (HD). 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. In an in vivo model, left carotid artery ligation was done in 7-day-old SD rat pups. The animals were divided into six groups; hypoxia (N),hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with dizocilpine (HD). Hypoxia was made by exposure to a 2 hour period of hypoxic incubator (92% N2, 8% O2). Results: In the in vitvo and in vivo models, the expressions of Bcl-2 in the hypoxia groups were reduced compared to the normoxia group. whereas those in the dizocilpine-treated group were increased compared to the hypoxia group. However. the expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were revealed reversely. Conclusion: Dizocilpine has neuroprotective property over perinatal HI brain injury via anti-apoptosis.
Abstract
Purpose: Current studies have demonstrated the neuroprotective effects of dizocilpine (MK-801) 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 dizocilpine can protect the developing rat brain from HI injury via anti-apoptosis. Methods: In an in vitro model, embryonic cortical neuronal cell culture of Sprague-Dawley (SD) rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with dizocilpine (HD). 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. In an in vivo model, left carotid artery ligation was done in 7-day-old SD rat pups. The animals were divided into six groups; hypoxia (N),hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with dizocilpine (HD). Hypoxia was made by exposure to a 2 hour period of hypoxic incubator (92% N2, 8% O2). Results: In the in vitvo and in vivo models, the expressions of Bcl-2 in the hypoxia groups were reduced compared to the normoxia group. whereas those in the dizocilpine-treated group were increased compared to the hypoxia group. However. the expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were revealed reversely. Conclusion: Dizocilpine has neuroprotective property over perinatal HI brain injury via anti-apoptosis.
참고문헌 (40)
- Amir G, "Neonatal brain protection and deep hypothermic circulatory arrest: pathophysiology of ischemic neuronal injury and protective strategies", Ann Thorac Surg, 80, pp.1955~1964 (2005)
- Choi DW, "Cerebral hypoxia: some new approaches and unanswered questions", J Neurosci, 10, pp.2493~2501 (1990)
- Garthwaite J, "Nitric oxide signaling in the central nervous system", Annu Rev Physiol, 57, pp.683~706 (1995)
- Marini AM, "Activity-dependent release of brain-derived neurotrophic factor underlies the neuroprotective effect of N-methyl-D-aspartate", J Biol Chem, 273, pp.29394~29399 (1998)
- Mukhin AG, "New in vitro model of traumatic neuronal injury: evaluation of secondary injury and glutamate receptor-mediated neurotoxicity", J Neurotrauma, 14, pp.651~663 (1997)
- Ayala GX, "Late N-methyl-D-aspartate receptor blockade rescues hippocampal neurons from excitotoxic stress and death after 4-aminopyridine-induced epilepsy", Eur J Neurosci, 22, pp.3067~3076 (2005)
- Kocaeli H, "MK-801 improves neurological and histological outcomes after spinal cord ischemia induced by transient aortic cross-clipping in rats", Surg Neurol, 64(Suppl 2), pp.22~27 (2005)
- Ford LM, "MK-801 prevents hippocampal neurodegeneration in neonatal hypoxicischemic rats", Arch Neurol, 46, pp.1090~1096 (1989)
- Han RZ, "NMDA receptor antagonist MK-801 reduces neuronal damage and preserves learning and memory in a rat model of traumatic brain injury", Neurosci Bull, 25, pp.367~375 (2009)
- Jantas D, "Different mechanisms of NMDA-mediated protection against neuronal apoptosis: a stimuli-dependent effect", Neurochem Res, 34, pp.2040~2054 (2009)
- Lam TT, "Ameliorative effect of MK-801 on retinal ischemia", J Ocul Pharmacol Ther, 13, pp.129~137 (1997)
- Lam TT, "N-methyl-D-aspartate (NMDA)--induced apoptosis in rat retina", Invest Ophthalmol Vis Sci, 40, pp.2391~2397 (1999)
- Zhang X, "MK-801 induces apoptotic neuronal death in the rat retrosplenial cortex: prevention by cycloheximide and R(-)-2-hexyl-N-methylpropargylamine", J Neurosci Res, 46, pp.82~89 (1996)
- Brewer GJ, "Isolation and culture of adult rat hippocampal neurons", J Neurosci Methods, 71, pp.143~155 (1997)
- Vannucci RC, "A model of perinatal hypoxic-ischemic brain damage", Ann N Y Acad Sci, 835, pp.234~249 (1997)
- Feng Y, "Treatment with tamoxifen reduces hypoxic-ischemic brain injury in neonatal rats", Eur J Pharmacol, 484, pp.65~74 (2004)
- Greenwood K, "Magnesium sulfate treatment after transient hypoxia-ischemia in the newborn piglet does not protect against cerebral damage", Pediatr Res, 48, pp.346~350 (2000)
- Vannucci RC, "Rat model of perinatal hypoxic-ischemic brain damage", J Neurosci Res, 55, pp.158~163 (1999)
- MacDonald HM, "Neonatal asphyxia. I. Relationship of obstetric and neonatal complications to neonatal mortality in 38,405 consecutive deliveries", J Pediatr, 96, pp.898~902 (1980)
- Delivoria-Papadopoulos M, "Mechanisms of cerebral injury in perinatal asphyxia and strategies for prevention", J Pediatr, 132, pp.30~34 (1998)
- Weitzdoerfer R, "Perinatal asphyxia in the rat has lifelong effects on morphology, cognitive functions, and behavior", Semin Perinatol, 28, pp.249~256 (2004)
- Chan PH, "Mitochondrial dysfunction and oxidative stress as determinants of cell death", survival in stroke, 2005, pp.1042, 203~209
- Zipfel GJ, "Neuronal apoptosis after CNS injury: the roles of glutamate and calcium", J Neurotrauma, 17, pp.857~869 (2000)
- Clawson TF, "Hypoxia-ischemia-induced apoptotic cell death correlates with IGF-I mRNA decrease in neonatal rat brain", Biol Signals Recept, 8, pp.281~293 (1999)
- Bagenholm R, "Free radicals are formed in the brain of fetal sheep during reperfusion after cerebral ischemia", Pediatr Res, 43, pp.271~275 (1998)
- Giulian D, "Inflammatory glia mediate delayed neuronal damage after ischemia in the central nervous system", Stroke, 24(12 Suppl), pp.184~190 (1993)
- Graham EM, "Neonatal mice lacking functional Fas death receptors are resistant to hypoxic-ischemic brain injury", Neurobiol Dis, 17, pp.89~98 (2004)
- Allan SM, "Inflammation in central nervous system injury", Philos Trans R Soc Lond B Biol Sci, 358, pp.1669~1677 (2003)
- Huang SS, "Resveratrol reduction of infarct size in Long-Evans rats subjected to focal cerebral ischemia", Life Sci, 69, pp.1057~1065 (2001)
- Ashwal S, "Animal models of neonatal stroke", Curr Opin Pediatr, 13, pp.506~516 (2001)
- Vannucci RC, "Hypoxic-ischemic encephalopathy", Am J Perinatol, 17, pp.113~120 (2000)
- Towfighi J, "Influence of age on the cerebral lesions in an immature rat model of cerebral hypoxiaischemia: a light microscopic study", Brain Res Dev Brain Res, 100, pp.149~160 (1997)
- Wyllie AH, "Apoptosis and the regulation of cell numbers in normal and neoplastic tissues: an overview", Cancer Metastasis Rev, 11, pp.95~103 (1992)
- Gerschenson LE, "Apoptosis: a different type of cell death", FASEB J, 6, pp.2450~2455 (1992)
- Johnson EM Jr, "Molecular mechanisms of developmental neuronal death", Annu Rev Neurosci, 16, pp.31~46 (1993)
- Dong JW, "Intermittent hypoxia attenuates ischemia", reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2, Cell Res, pp.2003, 13[DOI]
- Wolter KG, "Movement of Bax from the cytosol to mitochondria during apoptosis", J Cell Biol, 139, pp.1281~1292 (1997)
- Thornberry NA, "Caspases: enemies within", Science, 281, pp.1312~1316 (1998)
- Porter AG, "Emerging roles of caspase-3 in apoptosis", Cell Death Differ, 6, pp.99~104 (1999)
- Qin ZH, "Stimulation of N-methyl-D-aspartate receptors induces apoptosis in rat brain", Brain Res, 725, pp.166~176 (1996)
