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Journal of Investigative Medicine:
doi: 10.231/JIM.0b013e3181e80c40
Original Articles

Erythropoietin Markedly Attenuates Brain Infarct Size and Improves Neurological Function in the Rat

Yuen, Chun-Man MD*; Leu, Steve PhD†; Lee, Fan-Yen MD‡; Yen, Chia-Hung PhD§; Lin, Yu-Chun PhD†; Chua, Sarah MD†; Chung, Sheng-Ying MD†; Chai, Han-Tan MD†; Sheu, Jiunn-Jye MD‡; Ko, Sheung-Fat MD∥; Sun, Cheuk-Kwan MD, PhD¶; Yip, Hon-Kan MD†

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Background: The impact of epoetin beta (recombinant human erythropoietin) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) induced by distal left internal carotid artery occlusion was investigated.

Methods: Adult male Sprague-Dawley rats (n = 30) were categorized into group 2 (IS only) and group 3 (IS plus intraperitoneal erythropoietin 5000 IU/kg at 0, 12, and 24 hours after IS). Healthy Sprague-Dawley rats (n = 10) served as group 1.

Results: Analysis of brain tissues showed larger BIA in group 2 than in group 3 (P < 0.001). Corner test identified highest frequency of left turn in group 2 (P < 0.05). The mRNA expressions of Bax, caspase 3, interleukin 18, toll-like receptor 4, and plasminogen activator inhibitor 1 were highest, whereas Bcl-2 was lowest in group 2 (P < 0.05). Lower CXCR4 and stromal cell-derived factor 1 expressions were noted in group 2 than in group 3 (P < 0.01). Immunohistofluorescence staining showed lower expressions of CXCR4, stromal cell-derived factor 1, von Willebrand factor, and doublecortin with higher number of apoptotic nuclei in group 2 than in group 3 (P < 0.001). Immunohistochemical staining demonstrated lower cellular proliferation and number of small vessels with higher glial fibrillary acid protein expression in group 2 than in group 3 (P < 0.01).

Conclusions: Erythropoietin significantly limited BIA and improved sensorimotor dysfunction after acute IS.

© 2010 American Federation for Medical Research


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