Systemic injection of recombinant human erythropoietin after focal cerebral ischemia enhances oligodendroglial and endothelial progenitor cells in rat brain.
10.5115/acb.2010.43.2.140
- Author:
Young Jae KIM
1
;
Yong Wook JUNG
Author Information
1. Department of Laboratory Medicine, Masansamsung Medical Center, School of Medicine, Sungkyunkwan University, Masan, Korea.
- Publication Type:Original Article
- Keywords:
Erythropoietin;
systemic administration;
oligodendroglial and endothelial progenitors
- MeSH:
Animals;
Blood Vessels;
Blood-Brain Barrier;
Brain;
Brain Ischemia;
Bromodeoxyuridine;
Choroid Plexus;
Erythropoietin;
Humans;
Lateral Ventricles;
Oligodendroglia;
Rats;
Stem Cells;
Stroke
- From:Anatomy & Cell Biology
2010;43(2):140-149
- CountryRepublic of Korea
- Language:English
-
Abstract:
Erythropoietin (EPO) has been demonstrated the ability of recombinant human erythropoietin (r-Hu-EPO), when administered intracerebro-ventricularly, to improve stroke outcome through the reduction of stroke damage. In a brain ischemic model, however, systemic administration of r-Hu-EPO has not been intensely investigated given that in general, large glycosylated molecules have been deemed incapable of crossing the blood-brain barrier. In this study, administration of r-Hu-EPO for 4 days, intraperitoneally after ischemia-reperfusion (I-R) increased the number of bromodeoxyuridine (BrdU)-positive cells in the penumbra (10.1+/-1.4, n=5, P<0.05) and in the subventricular zone (SVZ) of the lateral ventricle (LV) (25+/-2.7, n=5, P<0.05) as compared with those of I-R (penumbra: 2.5+/-0.7; SVZ of LV: 3.8+/-1.5). A significant increase of BrdU-positive cells in these areas was coincident with a strong immunoreactivity of oligodendrocyte progenitor cell marker (2', 3'-cyclic nucleotide 3'-phosphodiesterase). Furthermore, r-Hu-EPO administration increased the number of BrdU-positive cells in the choroid plexus (7.8+/-2.3, n=5, P<0.05) and in cerebral blood vessels (3.5+/-1.3, n=5, P<0.05) when compared with those of I-R (choroid plexus: 1.2+/-0.5; cerebral blood vessels: 0.6+/-0.1). These results suggest that, even when systemically administered, r-Hu-EPO may have therapeutic potential for stroke via the proliferation of oligodendroglial and endothelial progenitor cells.
