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Published in: Translational Stroke Research 1/2015

01-02-2015 | Original Article

Recombinant Human Erythropoietin Improves the Neurofunctional Recovery of Rats Following Traumatic Brain Injury via an Increase in Circulating Endothelial Progenitor Cells

Authors: Liang Wang, Xiaonan Wang, Hua Su, Zhenying Han, Huijie Yu, Dong Wang, Rongcai Jiang, Zhenlin Liu, Jianning Zhang

Published in: Translational Stroke Research | Issue 1/2015

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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.
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Metadata
Title
Recombinant Human Erythropoietin Improves the Neurofunctional Recovery of Rats Following Traumatic Brain Injury via an Increase in Circulating Endothelial Progenitor Cells
Authors
Liang Wang
Xiaonan Wang
Hua Su
Zhenying Han
Huijie Yu
Dong Wang
Rongcai Jiang
Zhenlin Liu
Jianning Zhang
Publication date
01-02-2015
Publisher
Springer US
Published in
Translational Stroke Research / Issue 1/2015
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-014-0362-x

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