Korean J Pediatr.  2009 Jan;52(1):105-110. 10.3345/kjp.2009.52.1.105.

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

• Kim HM
• Choe BH
• Kwon SH
• Sohn YK

• KMID: 2037345
• DOI: http://doi.org/10.3345/kjp.2009.52.1.105

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.

Keyword

Hypoxia; Ischemia; Brain; Erythropoietin; Deferoxamine; Iron

MeSH Terms

Animals
Anoxia
Asphyxia
Brain
Brain Injuries
Carotid Arteries
Deferoxamine
Erythropoietin
Free Radicals
Humans
Incidence
Infant
Infant Mortality
Injections, Intraperitoneal
Iron
Ischemia
Ligation
Neuroprotective Agents
Oxygen
Premedication
Rats
Deferoxamine
Erythropoietin
Free Radicals
Iron
Neuroprotective Agents
Oxygen