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Erythropoietin Markedly Attenuates Brain Infarct Size and Improves Neurological Function in the Rat
  1. Chun-Man Yuen, MD*,
  2. Steve Leu, PhD,
  3. Fan-Yen Lee, MD,
  4. Chia-Hung Yen, PhD§,
  5. Yu-Chun Lin, PhD,
  6. Sarah Chua, MD,
  7. Sheng-Ying Chung, MD,
  8. Han-Tan Chai, MD,
  9. Jiunn-Jye Sheu, MD,
  10. Sheung-Fat Ko, MD,
  11. Cheuk-Kwan Sun, MD, PhD,
  12. Hon-Kan Yip, MD
  1. From the *Division of Neurosurgery, Department of Surgery, †Division of Cardiology, Department of Internal Medicine, and ‡Division of Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung Hsien; §Department of Life Science, National Pingtung University of Science and Technology, Pingtung; and ∥Department of Radiology and ¶Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung Hsien, Taiwan.
  1. Received January 18, 2010, and in revised form May 3, 2010.
  2. Accepted for publication May 12, 2010.
  3. Reprints: Hon-Kan Yip, MD, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 123, Ta Pei Rd, Niao Sung Hsiang, Kaohsiung Hsien, 83301, Taiwan. E-mail: han.gung{at}msa.hinet.net; Cheuk-Kwan Sun, MD, PhD, Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, 123, Ta Pei Rd, Niao Sung Hsiang, Kaohsiung Hsien, 83301, Taiwan. E-mail: lawrence.c.k.sun{at}gmail.com.
  4. Drs. Yuen and Leu contributed equally to this work.
  5. Dr. Sun contributed equally to this work compared with the corresponding author.
  6. This study was supported by a program grant from the National Science Council, Taiwan, ROC (grant no. NSC-97-2314-B-182A-090-MY2).

Abstract

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.

Key Words
  • acute ischemic stroke
  • EPO treatment

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