title: Recombinant human erythropoietin offers neuroprotection through inducing endogenous erythropoietin receptor and neuroglobin in a neonatal rat model of periventricular white matter damage.
abstract: Recombinant human erythropoietin (rh-EPO) has been reported to have protective effects against brain injury. The purpose of this study was to evaluate the levels of erythropoietin receptor (EPOR) and neuroglobin (Ngb) in a neonatal rat model of periventricular white matter damage (PWMD), and to identify the relationship between the two proteins. On postnatal day 3 (P3), rats underwent permanent ligation of the right common carotid artery followed by 6% O2for 4h (HI) or sham operation and normoxic exposure (sham). Immediately after HI, rats received a single intraperitoneal injection of rh-EPO (5U/g) or saline. We assessed the expression level of Ngb and EPOR on postnatal days 5, 7, 10 and 14. EPOR in the HI rats was initially increased as compared to the sham rats at P5. Subsequently, EPOR expression decreased, but was maintained at a higher level than in sham rats from P7 to P14. In rh-EPO treated rats, the increase in EPOR was greater than in HI rats at P5. However, EPOR levels decreased sharply from P7 to P14. In HI rats, Ngb was increased compared to the sham rats from P5 to P14. Ngb levels were further upregulated after rh-EPO administration from P5 to P10 compared to HI rats. However, this upregulation decreased at P14. In conclusion, this study shows that EPOR and Ngb were upregulated, and both of them act as important coordinated neuroprotectors in rh-EPO treatment of PWMD. However, the two proteins exhibit different expression patterns.
authors.affiliation: Institute of Clinical and Nursing, Jiangsu Jiankang Vocational College, 69 Huangshan Ling Road, Pukou District, Nanjing 211800, Jiangsu, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, Zhongda Hospital, Southeast University, 87 Dingjia Qiao, Gulou District, Nanjing 210009, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Zhongda Hospital, Southeast University, 87 Dingjia Qiao, Gulou District, Nanjing 210009, Jiangsu, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipai Lou, Xuanwu District, Nanjing 210096, Jiangsu, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Zhongda Hospital, Southeast University, 87 Dingjia Qiao, Gulou District, Nanjing 210009, Jiangsu, China. Electronic address: qiaolixing@aliyun.com.
authors.forename: Lixing
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Department of Pediatrics, Zhongda Hospital, Southeast University, 87 Dingjia Qiao, Gulou District, Nanjing 210009, Jiangsu, China. Electronic address: familyjiang77777@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage* / Q000235:genetics; D005260:Female; D005914:Globins / Q000378:metabolism*; D007969:Leukomalacia, Periventricular / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000078787:Neuroglobin; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D005914:Globins
keywords: Erythropoietin; Erythropoietin receptor; Hypoxia-ischemia; Neuroglobin; Premature