KMID : 1237720100430020140
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Anatomy & Cell Biology 2010 Volume.43 No. 2 p.140 ~ p.149
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Systemic injection of recombinant human erythropoietin after focal cerebral ischemia enhances oligodendroglial and endothelial progenitor cells in rat brain
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Kim Young-Jae
Jung Yong-Wook
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Abstract
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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¡¾1.4, n=5, P<0.05) and in the subventricular zone (SVZ) of the lateral ventricle (LV) (25¡¾2.7, n=5, P<0.05) as compared with those of I-R (penumbra: 2.5¡¾0.7; SVZ of LV: 3.8¡¾1.5). 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¡¾2.3, n=5, P<0.05) and in cerebral blood vessels (3.5¡¾1.3, n=5, P<0.05) when compared with those of I-R (choroid plexus: 1.2¡¾0.5; cerebral blood vessels: 0.6¡¾0.1). 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.
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KEYWORD
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Erythropoietin, systemic administration, oligodendroglial and endothelial progenitors
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