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Neuroprotection by local intra-arterial infusion of erythropoietin after focal cerebral ischemia in rats.
Neurol Res. 2011 Jun; 33(5):520-8.NR

Abstract

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.

Authors+Show Affiliations

Cerebrovascular Diseases Research Institute, Beijing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21669122

Citation

Dang, Sha, et al. "Neuroprotection By Local Intra-arterial Infusion of Erythropoietin After Focal Cerebral Ischemia in Rats." Neurological Research, vol. 33, no. 5, 2011, pp. 520-8.
Dang S, Liu X, Fu P, et al. Neuroprotection by local intra-arterial infusion of erythropoietin after focal cerebral ischemia in rats. Neurol Res. 2011;33(5):520-8.
Dang, S., Liu, X., Fu, P., Gong, W., Yan, F., Han, P., Ding, Y., Ji, X., & Luo, Y. (2011). Neuroprotection by local intra-arterial infusion of erythropoietin after focal cerebral ischemia in rats. Neurological Research, 33(5), 520-8. https://doi.org/10.1179/016164111X13007856084287
Dang S, et al. Neuroprotection By Local Intra-arterial Infusion of Erythropoietin After Focal Cerebral Ischemia in Rats. Neurol Res. 2011;33(5):520-8. PubMed PMID: 21669122.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotection by local intra-arterial infusion of erythropoietin after focal cerebral ischemia in rats. AU - Dang,Sha, AU - Liu,Xiangrong, AU - Fu,Paul, AU - Gong,Wei, AU - Yan,Feng, AU - Han,Pingxin, AU - Ding,Yuchuan, AU - Ji,Xunming, AU - Luo,Yumin, PY - 2011/6/15/entrez PY - 2011/6/15/pubmed PY - 2012/5/9/medline SP - 520 EP - 8 JF - Neurological research JO - Neurol. Res. VL - 33 IS - 5 N2 - 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. SN - 1743-1328 UR - https://www.unboundmedicine.com/medline/citation/21669122/Neuroprotection_by_local_intra_arterial_infusion_of_erythropoietin_after_focal_cerebral_ischemia_in_rats_ L2 - http://www.tandfonline.com/doi/full/10.1179/016164111X13007856084287 DB - PRIME DP - Unbound Medicine ER -