Korean J Pediatr.  2010 Oct;53(10):898-908. 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

• Kim MS
• Seo YK
• Park HJ
• Lee KH
• Lee KH
• Choi EJ
• Kim JK
• Chung HL
• Kim WT

• KMID: 2011554
• DOI: http://doi.org/10.3345/kjp.2010.53.10.898

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.

Keyword

Erythropoietin; Apoptosis; Hypoxic-ischemic brain injury; Bcl-2; Bax; Caspase-3

MeSH Terms

Animals
Anoxia
Apoptosis
Brain
Brain Injuries
Carotid Arteries
Caspase 3
Cell Culture Techniques
Cells, Cultured
Erythropoietin
Humans
Models, Animal
Neurons
Neuroprotective Agents
Pregnancy
Rats
Caspase 3
Erythropoietin
Neuroprotective Agents