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.

Expression of ephrinB2 and EphB4 in a neonatal rat model of periventricular white matter damage

“…Study suggests that CD34 is a marker of mononuclear cells that maintain vascular integrity by producing endothelial progenitor cells [21]. Consistent with the spike of CD34 + cells in HI-induced PWMD that was previously published by our group [30], vessel-lumen structures were detected 4 days after HI. We observed that the CD34 + cells first appeared as single cells and then accumulated cell-cell contacts.…”

Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway

“…[1] Brain damage of prematurity is the predominant form of the acquired brain damage in neonates who undergo neurological morbidity. [2] There are only limited therapies to improve the outcome from the HIBD. [3] Administration of the recombinant human-erythropoietin (rh-EPO) into extremely preterm infants at Neonatal Intensive Care Unit improved neurodevelopmental outcomes.…”

“…The present study therefore used an animal model to investigate the role of rh-EPO in enhanced neurological recovery, which was thought to be related to the promotion of angiogenesis. [25]…”

Circular RNA Expression in the Brain of a Neonatal Rat Model of Periventricular White Matter Damage

“…As described in our previous study [28], postnatal day 3 (P3) rats underwent permanent ligation of the right common carotid artery after anesthetization with ether. Pups were returned to the home cage for 2 h, then exposed to hypoxia (94% N2 + 6% O2) for 2h by being placed in a sealed chamber partially submersed in a 37°C water bath.…”