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.

OBJECTIVES:

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: Lihua Zhu, Xiang Bai, Shiyu Wang, Yan Hu, Ting Wang, Lijuan Qian, Li Jiang
• Journal: Neonatology (Neonatology) Vol. 106 Issue 2 Pg. 143-8 ( 2014) ISSN: 1661-7819 [Electronic] Switzerland
• PMID: 24969821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Angiogenesis Inducing Agents
• Angiopoietin-1
• Angpt1 protein, rat
• Antigens, CD34
• EPO protein, human
• Neuroprotective Agents
• RNA, Messenger
• Recombinant Proteins
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat
• Erythropoietin

Topics

• Angiogenesis Inducing Agents (pharmacology)
• Angiopoietin-1 (genetics, metabolism)
• Animals
• Animals, Newborn
• Antigens, CD34 (metabolism)
• Brain (blood supply, drug effects, metabolism, physiopathology)
• Cytoprotection
• Disease Models, Animal
• Erythropoietin (pharmacology)
• Female
• Humans
• Hypoxia-Ischemia, Brain (genetics, metabolism, physiopathology, prevention & control)
• Neovascularization, Physiologic (drug effects)
• Neuroprotective Agents (pharmacology)
• Pregnancy
• RNA, Messenger (metabolism)
• Rats, Sprague-Dawley
• Recombinant Proteins (pharmacology)
• Time Factors
• Vascular Endothelial Growth Factor A (genetics, metabolism)