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The effect of erythropoietin in neonatal rat model of hypoxic-ischemic brain injury

Korean Journal of Pediatrics 2009;52(1):105-110.
Published online January 15, 2009.
The effect of erythropoietin in neonatal rat model of hypoxic-ischemic brain injury
Heng-Mi Kim1, Byung-Ho Choe1, Soon-Hak Kwon1, Yoon-Kyung Sohn2
1Department of Pediatrics, College of Medicine, Kyungpook National University, Daegu, Korea
2Department of Pathology, College of Medicine, Kyungpook National University, Daegu, Korea
Erythropoietin의 투여가 신생백서 저산소허혈뇌손상에 미치는 영향
김행미1, 최병호1, 권순학1, 손윤경2
1경북대학교 의과대학 소아과학교실
2경북대학교 의과대학 병리학교실
Correspondence: 
Heng-Mi Kim, Email: hmkim@knu.ac.kr
Abstract
Purpose
: Perinatal asphyxia is an important cause of neonatal mortality and subsequent lifelong neurodevelopmental handicaps. Although many treatment strategies have been tested, there is currently no clinically effective treatment to prevent or reduce the harmful effects of hypoxia and ischemia in humans. Erythropoietin (Epo) has been shown to exert neuroprotective effects in various brain injury models although the exact mechanisms through which Epo functions are not completely understood. This study investigates the effect of Epo on hypoxic-ischemic (HI) brain injury and the possibility that its neuroprotective actions may be associated with iron-mediated metabolism.
Methods
: HI brain injury was produced in 7-day-old rats by unilateral carotid artery ligation followed by hypoxia with 8% oxygen for 2 h. At the end of HI brain injury, the rats received an intraperitoneal injection of 5,000 units/kg erythropoietin. Random premedication with iron, deferoxamine, iron-deferoxamine, or saline were performed 23 d before HI brain injury. The severity of the brain injury was assessed at 7 d after HI.
Results
: Single Epo treatment post-HI brain injury reduced the gross and histopathological findings of brain injury. Iron premedication did not increase the incidence or severity of the injury as measured by the damage score. Deferoxamine administration before HI brain injury improved the brain injury as compared to no treatment or Epo treatment.
Conclusion
: These findings indicate that Epo provides neuroprotective benefits after HI in the developing brain. These findings suggest that Epos neuroprotective actions may involve reducing iron in tissues that mediate the formation of free radicals.
Key Words: Hypoxia, Ischemia, Brain, Erythropoietin, Deferoxamine, Iron


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