title: Recombinant human erythropoietin improves the neurofunctional recovery of rats following traumatic brain injury via an increase in circulating endothelial progenitor cells.
abstract: Previous studies show that circulating endothelial progenitor cells (EPCs) promote angiogenesis, which is a process associated with improved recovery in animal models of traumatic brain injury (TBI), and that recombinant human erythropoietin (rhEPO) plays a protective role following stroke. Thus, it was hypothesized that rhEPO would enhance recovery following brain injury in a rat model of TBI via an increase in the mobilization of EPCs and, subsequently, in angiogenesis. Flow cytometry assays using CD34- and CD133-specific antibodies were utilized to identify alterations in EPC levels, CD31 and CD34 antibody-stained brain tissue sections were used to quantify angiogenesis, and the Morris water maze (MWM) test and the modified Neurological Severity Score (mNSS) test were used to evaluate behavioral recovery. Compared with saline treatment, treatment with rhEPO significantly increased the number of circulating EPCs on days 1, 4, 7, and 14 (P < 0.05), improved spatial learning ability on days 24 and 25 (P < 0.05), and enhanced memory recovery on day 26 (P < 0.05). Moreover, rhEPO treatment decreased mNSS assessment scores on days 14, 21, and 25 (P < 0.05). There was a strong correlation between levels of circulating EPCs and CD34- and CD31-positive cells within the injured boundary zone (CD34(+) r = 0.910, P < 0.01; CD31(+) r = 0.894, P < 0.01) and the ipsilateral hippocampus (CD34(+) r = 0.841, P < 0.01; CD31(+) r = 0.835, P < 0.01). The present data demonstrate that rhEPO treatment improved functional outcomes in rats following TBI via an increase in the mobilization of EPCs and in subsequent angiogenesis.
authors.affiliation: Department of Neurosurgery, Tianjin 5th Center Hospital, Number 41 Zhejiang Road, Tanggu District, Tianjin, 300450, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.forename: Zhenying
authors.initials: Z
authors.lastname: Han
authors.forename: Huijie
authors.initials: H
authors.lastname: Yu
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Rongcai
authors.initials: R
authors.lastname: Jiang
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Liu
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage*; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology*; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000502:physiology*; D004921:Erythropoietin / Q000008:administration & dosage*; D006400:Hematocrit; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage; D020127:Recovery of Function; D065853:Spatial Learning / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; C554270:EPO protein, human; D011994:Recombinant Proteins; D004921:Erythropoietin
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