Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 88, Issue 14, Pages 3206-3214Publisher
WILEY
DOI: 10.1002/jnr.22470
Keywords
brain atrophy; cerebral tissue repair; erythropoietin; embolic stroke; magnetic resonance imaging
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Funding
- NINDS [PO1 NS23393, PO1 NS42345, RO1 NS43324, RO1 NS48349]
- Mort and Brigitte Harris Foundation
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Using magnetic resonance imaging (MRI) protocols of T2-, T-2-(*), diffusion-and susceptibility-weighted imaging (T2WI, (T2WI)-W-*, DWI, and SWI, respectively) with a 7T system, we tested the hypothesis that treatment of embolic stroke with erythropoietin (EPO) initiated at 24 hr and administered daily for 7 days after stroke onset has benefit in repairing ischemic cerebral tissue. Adult Wistar rats were subjected to embolic stroke by means of middle cerebral artery occlusion (MCAO) and were randomly assigned to a treatment (n = 11) or a control (n 5 11) group. The treated group was given EPO intraperitoneally at a dose of 5,000 IU/kg daily for 7 days starting 24 hr after MCAO. Controls were given an equal volume of saline. MRI was performed at 24 hr and then weekly for 6 weeks. MRI and histological measurements were compared between groups. Serial T2WI demonstrated that expansion of the ipsilateral ventricle was significantly reduced in the EPO-treated rats. The volume ratio of ipsilateral parenchymal tissue relative to the contralateral hemisphere was significantly increased after EPO treatment compared with control animals, indicating that EPO significantly reduces atrophy of the ipsilateral hemisphere, although no significant differences in ischemic lesion volume were observed between the two groups. Angiogenesis and white matter remodeling were significantly increased and occurred earlier in EPO-treated animals than in the controls, as evident from (T2WI)-W-* and diffusion anisotropy maps, respectively. These data indicate that EPO treatment initiated 24 hr poststroke promotes angiogenesis and axonal remodeling in the ischemic boundary, which may potentially reduce atrophy of the ipsilateral hemisphere. (c) 2010 Wiley-Liss, Inc.
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