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Neuroprotection by local intra-arterial infusion of erythropoietin after focal cerebral ischemia in rats.
MedLine Citation:
PMID:  21669122     Owner:  NLM     Status:  In-Data-Review    
OBJECTIVES: The neuroprotective effect of erythropoietin has been demonstrated by ischemia and reperfusion models in adult and neonatal rodents. However, administration of high-dose erythropoietin has potential complications. The goal of this study was to determine whether local infusion of low dose erythropoietin offers neuroprotective effects after ischemia and reperfusion injury.
METHODS: Adult male Sprague-Dawley rats subject to middle cerebral artery occlusion were randomly divided into three groups: (1) sham group: the rats received the same procedure as the other two groups except that no suture was inserted; (2) vehicle group: intra-artery local infusion of saline was administered via middle cerebral artery after reperfusion; and (3) treatment group: 50 U/kg intra-artery local infusion of erythropoietin was administered via middle cerebral artery after reperfusion. Neurological deficit scores and infarct volume (determined by hematoxylin-eosin staining) were evaluated 48 hours after reperfusion. Apoptosis was measured through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression of vascular endothelial growth factor and phosphorylated extracellular signal-regulated kinase were investigated by immunohistochemistry method.
RESULTS: The results show that intra-artery local infusion of erythropoietin, via the middle cerebral artery, significantly reduced neurological deficit scores, foot fault number, and the infarct volume at 48 hours after reperfusion. Significant reductions were also found in the number of positive cells stained by TUNEL assay within the ischemic core and penumbra. Furthermore, local infusion of erythropoietin increased the expression of phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor.
DISCUSSION: Local infusion of low-dose erythropoietin via the middle cerebral artery is shown to be neuroprotective against cerebral ischemia and reperfusion injury. The mechanism of neuroprotection may be associated with the increased expression of phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor.
Sha Dang; Xiangrong Liu; Paul Fu; Wei Gong; Feng Yan; Pingxin Han; Yuchuan Ding; Xunming Ji; Yumin Luo
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neurological research     Volume:  33     ISSN:  1743-1328     ISO Abbreviation:  Neurol. Res.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905298     Medline TA:  Neurol Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  520-8     Citation Subset:  IM    
Cerebrovascular Diseases Research Institute, Beijing, China.
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