Erythropoietin markedly attenuates brain infarct size and improves neurological function in the rat.
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.
Yuen
Chun-Man
CM
Division of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung Hsien, Taiwan.
Leu
Steve
S
Lee
Fan-Yen
FY
Yen
Chia-Hung
CH
Lin
Yu-Chun
YC
Chua
Sarah
S
Chung
Sheng-Ying
SY
Chai
Han-Tan
HT
Sheu
Jiunn-Jye
JJ
Ko
Sheung-Fat
SF
Sun
Cheuk-Kwan
CK
Yip
Hon-Kan
HK
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020520:Brain Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004660:Encephalitis / Q000188:drug therapy / Q000473:pathology; D004921:Erythropoietin / Q000494:pharmacology*; D006397:Hematinics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D020127:Recovery of Function / Q000187:drug effects*
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D006397:Hematinics; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin