title: Erythropoietin improves brain development in short-term hypoxia in rat embryo cultures.
abstract: BACKGROUND
  Hypoxic ischemic encephalopathy continues to be a significant cause of death and disability worldwide. Erythropoietin (EPO) has the potential to lessen neurologic sequelae due to hypoxia-ischemia.
  
  
  METHODS
  The in vitro effects of EPO on total embryonic development and brain VEGF receptor (VEGFR) expressions were investigated in 50 rat embryos at 9.5 days of gestation that were cultured in whole rat serum (WRS). According to the study protocol, the embryos were divided into two groups. The first group is comprised hypoxia, 100 and 50 U/ml EPO after hypoxia groups. Group 2 comprised control (WRS) and WRS+EPO. After 48-h culture, the embryos from each group were harvested to be analyzed according to a morphological scoring system and also genetically to measure brain VEGFR expression.
  
  
  RESULTS
  The mean morphological scores for the embryos grown in control, WRS+EPO, hypoxia, and in the presence of 100 and 50 U/ml EPO in hypoxic medium were 55.30±7.22, 52.10±5.27, 23.0±4.60, 36.20±5.07, and 19.70±5.07, respectively. Expressions of VEGFR-1, -2, -3 were significantly elevated in the 100U/ml EPO and WRS+EPO groups compared to the hypoxia group (p<0.05).
  
  
  CONCLUSIONS
  These results support the conclusion that (1) VEGFR-1, -2, -3 may increase with EPO treatment in hypoxic conditions, (2) VEGF and EPO may be part of a self-regulated physiological protection mechanism to prevent neuronal injury including in utero neural tube defects.
authors: Erciyes University, Faculty of Medicine, Department of Pediatric Hematology, 38039 Kayseri, Turkey. Electronic address: yaseminaltuner@yahoo.com.
authors: Yasemin Altuner
authors: YA
authors: Torun
authors: Erciyes University, Faculty of Medicine, Department of Pediatric Hematology, 38039 Kayseri, Turkey.
authors: Mehmet Akif
authors: MA
authors: Ozdemir
authors: Erciyes University, Faculty of Medicine, Department of Anatomy and Clinical Research Institute, 38039 Kayseri, Turkey.
authors: Harun
authors: H
authors: Ulger
authors: Erciyes University, Faculty of Medicine, Department of Anatomy and Clinical Research Institute, 38039 Kayseri, Turkey.
authors: Mehtap
authors: M
authors: Nisari
authors: Erciyes University, Faculty of Medicine, Department of Genetics, 38039 Kayseri, Turkey.
authors: Hilal
authors: H
authors: Akalın
authors: Erciyes University, Faculty of Medicine, Department of Pediatric Hematology, 38039 Kayseri, Turkey.
authors: Turkan
authors: T
authors: Patıroglu
authors: Erciyes University, Faculty of Medicine, Department of Genetics, 38039 Kayseri, Turkey.
authors: Yusuf
authors: Y
authors: Ozkul
authors: Erciyes University, Faculty of Medicine, Department of Genetics, 38039 Kayseri, Turkey.
authors: Muge
authors: M
authors: Onal
authors: Erciyes University, Faculty of Medicine, Department of Pediatric Hematology, 38039 Kayseri, Turkey.
authors: Musa
authors: M
authors: Karakukcu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000196:embryology; D004921:Erythropoietin / Q000627:therapeutic use*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy* / Q000473:pathology*; D066298:In Vitro Techniques; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D004921:Erythropoietin; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Brain development; Embryo cultures; Erythropoietin; Hypoxia