Perinatology.  2017 Sep;28(3):79-91. 10.14734/PN.2017.28.3.79.

Recombinant Human Erythropoietin Exerts Neuroprotective Effects via Modulation of Nitric Oxide Synthase on Hypoxic-Ischemic Brain Injury in Neonatal Rats

Affiliations
  • 1Department of Pediatrics, Catholic University of Daegu School of Medicine, Daegu, Korea. wootykim@hanmail.net
  • 2Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Korea.

Abstract


OBJECTIVE
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 there are limited the same consequences occurring during neonatal periods. Here, we investigated whether recombinant human EPO (rHuEPO) can protect the developing rat brain from HI injury via the modulation of nitric oxide synthase.
METHODS
The in vitro model involved culturing embryonic cortical neuronal cells of Sprague-Dawley (SD) rats at 19 days gestation. The cultured cells were divided into five groups: normoxia (N), hypoxia (H), 1, 10 and 100 IU/mL rHuEPO-treated (H+E1, H+E10, and H+E100). In the in vivo model, left carotid artery ligation was performed in 7-day-old SD rat pups. The animals were divided into six groups: normoxia control, normoxia Sham-operated, hypoxia only (H), hypoxia+vehicle, hypoxia+ rHuEPO before a hypoxic insult (HE-B), and hypoxia+rHuEPO after a hypoxic insult (HE-A). Western blotting and real-time polymerase chain reaction using antibodies and primers of inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS) were performed.
RESULTS
The rHuEPO-treated group in the in vitro model showed increased expressions of iNOS and eNOS and decreased expression of nNOS compared to those of the H group. In the HE-A and HE-B groups of the in vivo model of the, the results were similar as aforementioned.
CONCLUSION
rHuEPO exerts neuroprotective properties over perinatal HI brain injuries through the modulation of nitric oxide synthase.

Keyword

Erythropoietin; Nitric oxide synthase; Hypoxia-ischemia; Brain
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