title: Systemic injection of recombinant human erythropoietin after focal cerebral ischemia enhances oligodendroglial and endothelial progenitor cells in rat brain.
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.
authors.affiliation: Department of Laboratory Medicine, Masansamsung Medical Center, School of Medicine, Sungkyunkwan University, Masan, Korea.
authors.forename: Young Jae
authors.initials: YJ
authors.lastname: Kim
authors.forename: Yong-Wook
authors.initials: YW
authors.lastname: Jung