title: Recombinant human erythropoietin augments angiogenic responses in a neonatal rat model of cerebral unilateral hypoxia-ischemia.
abstract: BACKGROUND
  Recombinant human erythropoietin (rh-EPO) has been used as a drug to treat premature infant anemia for over a decade. In addition to its erythropoietic effect, rh-EPO has also been reported to have protective effects against brain injury.
  
  
  OBJECTIVE
  Our aim was to evaluate the levels of angiogenesis-related cells (CD34+ cells) and angiogenic factors (vascular endothelial growth factor, VEGF, and angiopoietin-1, Ang-1) in a neonatal rat model of cerebral unilateral hypoxia-ischemia (HI) and to identify the effects of rh-EPO on angiogenic responses.
  
  
  METHODS
  Postnatal day 3 (PD3) rats underwent permanent ligation of the right common carotid artery followed by 6% O2 for 4 h (HI) or sham operation and normoxic exposure (sham). Immediately after HI, the rats received a single intraperitoneal injection of rh-EPO (5 U/g) or saline. Angiogenesis-related cells (CD34+ cells) and angiogenic factors (VEGF and Ang-1) were examined on PD5, 7, 10 and 14.
  
  
  RESULTS
  Compared with the sham rats, the number of CD34+ cells in HI rats increased from PD5 to 7 but decreased from PD10 to 14. VEGF and Ang-1 mRNA levels both increased from PD5 to 14. CD34+ cells, VEGF and Ang-1 were all upregulated in rh-EPO-treated rats compared with HI rats.
  
  
  CONCLUSIONS
  In the present study, we show the angiogenic effects of rh-EPO in a rat model of neonatal cerebral unilateral HI. Our results highlight the powerful therapeutic potential of rh-EPO treatment of HI premature brain for the enhancement of angiogenic responses.
authors: Research Center for Learning Science, Clinical Medical College, Nanjing, China.
authors: Lihua
authors: L
authors: Zhu
authors: Xiang
authors: X
authors: Bai
authors: Shiyu
authors: S
authors: Wang
authors: Yan
authors: Y
authors: Hu
authors: Ting
authors: T
authors: Wang
authors: Lijuan
authors: L
authors: Qian
authors: Li
authors: L
authors: Jiang
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D018952:Antigens, CD34 / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D019610:Cytoprotection; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; C467629:Angpt1 protein, rat; D018952:Antigens, CD34; C554270:EPO protein, human; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004921:Erythropoietin