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ORIGINAL ARTICLE
Korean J Pediatr 2010 October;53(10) :898-908.
doi:https://doi.org/10.3345/kjp.2010.53.10.898
The neuroprotective effect of recombinant human erythropoietin via an antiapoptotic mechanism on hypoxic-ischemic brain injury in neonatal rats
Moon Sun Kim (Kim MS)1, Yoo Kyung Seo (Seo YK)2, Hye Jin Park (Park HJ)2, Kye Hyang Lee (Lee KH)2, Kyung Hoon Lee (Lee KH)2, Eun Jin Choi (Choi EJ)2, Jin Kyung Kim (Kim JK)2, Hai Lee Chung (Chung HL)2, Woo Taek Kim (Kim WT)1
1Department of Pediatrics, School of Medicine, Catholic University of Daegu, Korea
2Department of Pediatrics, Dongguk University College of Medicine, Gyeongju, Gyungsangbookdo, Korea
Corresponding Author: Woo Taek Kim ,Email: wootykim@cu.ac.kr
Copyright © 2010 by The Korean Pediatric Society
ABSTRACT
Purpose : The neuroprotective effects of erythropoietin (EPO) have been recently shown in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity; however, limited data are available for such effects during the neonatal periods. Therefore, we investigated whether recombinant human EPO (rHuEPO) can protect against perinatal HI brain injury via an antiapoptotic mechanism. Methods : The left carotid artery was ligated in 7-day-old Sprague- Dawley (SD) rat pups (in vivo model). The animals were divided into 6 groups: normoxia control (NC), normoxia sham-operated (NS), hypoxia only (H), hypoxia+vehicle (HV), hypoxia+rHuEPO before a hypoxic insult (HE-B), and hypoxia+rHuEPO after a hypoxic insult (HE-A). Embryonic cortical neuronal cell culture of SD rats at 18 days gestation (in vitro model) was performed. The cultured cells were divided into 5 groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated groups. Results : In the in vivo model, Bcl-2 expressions in the H and HV groups were lower than those in the NC and NS groups, whereas those in the HE-A and HE-B groups were greater than those of the H and HV groups. The expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were in contrast to those of Bcl-2. In the in vitro model, the patterns of Bcl-2, Bax, and caspase-3 expression and Bax/Bcl-2 ratio were similar to the results obtained in the in vivo model. Conclusion : rHuEPO exerts neuroprotective effect against perinatal HI brain injury via an antiapoptotic mechanism.
Keywords: Erythropoietin | Apoptosis | Hypoxic-ischemic brain injury | Bcl-2 | Bax | Caspase-3
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