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논문 기본 정보

자료유형
학술저널
저자정보
저널정보
대한신생아학회 Neonatal medicine Neonatal medicine 제16권 제2호
발행연도
2009.1
수록면
221 - 233 (13page)

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Purpose : Erythropoietin (EPO) has neuroprotective effects in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity. Current studies have demonstrated the neuroprotective effects of EPO, but limited data are available for the neonatal periods. Here in we investigated whether recombinant human EPO (rHuEPO) can protect the developing rat brain from HI injury via modulation of NMDA receptors. Methods : In an in vitro model, embryonic cortical neuronal cell cultures from Sprague- Dawley (SD) rats at 19-days gestation were established. The cultured cells were divided into five groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated (H+E1, H+ E10, and H+E100) groups. To estimate cell viability and growth, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was done. In an in vivo model, left carotid artery ligation was performed on 7-day-old SD rat pups. The animals were divided into six groups; normoxia control (NC), normoxia Sham-operated (NS), hypoxia- ischemia only (H), hypoxia-ischemia+vehicle (HV), hypoxia-ischemia+rHuEPO before a HI injury (HE-B), and hypoxia-ischemia+rHuEPO after a HI injury (HE-A). The morphologic changes following brain injuries were noted using hematoxylin and eosin (H/E) staining. Real-time PCR using primers of subunits of NMDA receptors (NR1, NR2A, NR2B, NR2C and NR2D) mRNA were performed. Results : Cell viability in the H group was decreased to less than 60% of that in the N group. In the H+E1 and H+E10 groups, cell viability was increased to >80% of the N group, but cell viability in the H+E100 group did not recover. The percentage of the left hemisphere area compared the to the right hemisphere area were 98.9% in the NC group, 99.1% in the NS group, 57.1% in the H group, 57.0% in the HV group, 87.6% in the HE-B group, and 91.6% in the HE-A group. Real-time PCR analysis of the expressions of subunits of NMDA receptors mRNAs in the in vitro and in vivo neonatal HI brain injuries generally revealed that the expression in the H group was decreased compared to the N group and the expressions in the rHuEPO-treated groups was increased compared to the H group. Conclusion : rHuEPO has neuroprotective property in perinatal HI brain injury via modulation of N-methyl-D-aspartate receptors.
#Erythropoietin #N-methyl-D-aspartate receptor #Hypoxic-ischemic brain injury

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참고문헌 (24)

참고문헌 신청
Anderson P / 2003 / Victorian Infant Collaborative Study Group Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990s / google schola Ashwal S / 2001 / Animal mo google schola Atlason PT / 2007 / N-Methyl-D-aspartate (NMDA) receptor subunit NR1 forms the substrate for oligomeric assembly of the NMDA receptor / J Biol Chem 282 : 25299 ~ 25307 google schola Brewer GJ / 1997 / Isolation and culture of adult rat hippocampal neurons / J Neurosci Meth 71 : 143 ~ 155 google schola Calapai G / 2000 / Erythropoietin protects against brain ischemic injury by inhibition of nitric oxide formation / Eur J Pharmacol 401 : 349 ~ 356 google schola

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