Mechanism of Erythropoietin-induced hypoxic-ischemic brain injury protection.

CHEN Qin-ling; JIANG Hui-ying; YANG Mei; LI Xiao-dong; ZHAO Xiao-li.

doi:10.11852/zgetbjzz2016-24-08-12

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Chinese Journal of Child Health Care ›› 2016, Vol. 24 ›› Issue (8) : 825-828. DOI: 10.11852/zgetbjzz2016-24-08-12

Mechanism of Erythropoietin-induced hypoxic-ischemic brain injury protection.

CHEN Qin-ling¹,JIANG Hui-ying¹,YANG Mei¹,LI Xiao-dong²,ZHAO Xiao-li².

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Abstract

Objective To assess the expression levels of excitatory amino acid transporter 2 (EAAT2) in classical rat model of hypoxic ischemic encephalopathy (HIE),and the expression level of that after erythropoietin (EPO) treatment. Methods Totally,108 postnatal 72 h SD rats were randomly assigned into six groups,including control,hypoxia,ischemia,hypoxia-ischemia,EPO treatment,and saline treatment.A neonatal rat model of HIE by bilateral ligation of carotid artery and subsequent anaerobic treatment for 2 hrs was constructed.The behavior of rats was recorded.The expression level of EAAT2 was assessed by Western blotting.Moreover,mRNA levels of EAAT1 and EAAT2 was measured using real time polymerase chain reaction. Results Typical HIE characteristics were observed on the models.The mRNA level of EAAT1 and expression level of EAAT2 was obviously reduced after hypoxia,ischemia,and hypoxia-ischemia.After treatment by EPO,the expression levels of EAAT1 and EAAT2 increased.Moreover,the gene expression levels in cortex were higher than that in hippocampe. Conclusion Reduced EAAT2 expression levels may be one reason for the development of HIE,which might also contribute to the curative effect of EPO.

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CHEN Qin-ling,JIANG Hui-ying,YANG Mei,LI Xiao-dong,ZHAO Xiao-li.. Mechanism of Erythropoietin-induced hypoxic-ischemic brain injury protection.[J]. Chinese Journal of Child Health Care. 2016, 24(8): 825-828 https://doi.org/10.11852/zgetbjzz2016-24-08-12

References

[1] Tagin M,Abdel-Hady H,ur Rahman S,et al:Neuroprotection for perinatal hypoxic ischemic encephalopathy in low- and middle-income countries[J].The Journal of Pediatrics,2015,167(1):25-28.
[2] Xu T,Li W,Liang Y,et al.Neuroprotective effects of electro acupuncture on hypoxic-ischemic encephalopathy in newborn rats Ass[J].Pakistan Journal of Pharmaceutical Sciences,2014,27(6):1991-2000.
[3] 王钰.促红细胞生成素在新生儿缺氧缺血性脑病中的研究进展[J].中国儿童保健杂志,2011,19(8):3.
[4] Rocamonde B,Paradells S,Barcia JM,et al:Neuroprotection of lipoic acid treatment promotes angiogenesis and reduces the glial scar formation after brain injury[J].Neuroscience,2012,224(1):102-115.
[5] Kim MS,Seo YK,Park HJ,et al:The neuroprotective effect of recombinant human erythropoietin via an antiapoptotic mechanism on hypoxic-ischemic brain injury in neonatal rats[J].Korean Journal of Pediatrics,2010,53(10):898-908.
[6] Sun Y,Zhou C,Polk P,et al:Mechanisms of erythropoietin-induced brain protection in neonatal hypoxia-ischemia rat model[J].Journal of Cerebral Blood Flow and Metabolism:Official Journal of the International Society of Cerebral Blood Flow and Metabolism,2004,24 (2):259-270.
[7] Suzuki M,Nelson AD,Eickstaedt JB,et al:Glutamate enhances proliferation and neurogenesis in human neural progenitor cell cultures derived from the fetal cortex[J].The European Journal of Neuroscience,2006,24 (3):645-653.
[8] Shigeri Y,Seal RP,Shimamoto K.Molecular pharmacology of glutamate transporters,EAATs and VGLUTs[J].Brain Research Reviews,2004,45 (3):250-265.
[9] Rao VL,Dogan A,Todd KG,et al.Antisense knockdown of the glial glutamate transporter GLT-1,but not the neuronal glutamate transporter EAAC1,exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain[J].The Journal of Neuroscience:the Official Journal of the Society for Neuroscience,2001,21(6):1876-1883.
[10] Gilley JA,Kernie SG.Excitatory amino acid transporter 2 and excitatory amino acid transporter 1 negatively regulate calcium-dependent proliferation of hippocampal neural progenitor cells and are persistently upregulated after injury[J].The European Journal of Neuroscience,2011,34 (11):1712-1723.
[11] Sampath D,White AM,Raol YH.Characterization of neonatal seizures in an animal model of hypoxic-ischemic encephalopathy[J].Epilepsia,2014,55 (7):985-993.
[12] Steck J,Blueml C,Kampmann S,et al.Retinal vessel pathologies in a rat model of periventricular leukomalacia:a new model for retinopathy of prematurity?[J] Investigative Ophthalmology & Visual Science,2015,56(3):1830-1841. [13] Holmseth S,Scott HA,Real K,et al.The concentrations and distributions of three C-terminal variants of the GLT1 (EAAT2; slc1a2) glutamate transporter protein in rat brain tissue suggest differential regulation[J].Neuroscience,2009,162 (4):1055-1071.
[14] Chretien F,Le Pavec G,Vallat-Decouvelaere AV,et al:Expression of excitatory amino acid transporter-1 (EAAT-1) in brain macrophages and microglia of patients with prion diseases[J].Journal of Neuropathology and Experimental Neurology,2004,63 (10):1058-1071.
[15] 吴英丽:促红细胞生成素在新生儿的应用进展[J].中国儿童保健杂志,2011,19 (9):3.
[16] 陈广斌 ,张毅,陆羡.促红细胞生成素对新生鼠缺血缺氧性脑损伤保护作用的研究[J].中国儿童保健杂志,2006,14 (4):3.
[17] Kawakami M,Sekiguchi M,Sato K,et al:Erythropoietin receptor-mediated inhibition of exocytotic glutamate release confers neuroprotection during chemical ischemia[J].The Journal of Biological Chemistry,2001,276 (42):39469-39475.
[18] Sims B,Clarke M,Njah W,et al:Erythropoietin-induced neuroprotection requires cystine glutamate exchanger activity[J].Brain Research,2010,1321:88-95.
[19] Langford MP,Redens TB,Liang C,et al:EAAT and Xc exchanger inhibition depletes glutathione in the transformed human lens epithelial cell line SRA 01/04[J].Current Eye Research,2015,41(3):1-10.