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Table of Contents
Vol. 30, No. 4, 2008
Issue release date: May 2008
Section title: Original Paper
Dev Neurosci 2008;30:231–242
(DOI:10.1159/000110348)

Recombinant Erythropoietin Is Neuroprotective in a Novel Mouse Oxidative Injury Model

Juul S.E.a · McPherson R.J.a · Bammler T.K.b · Wilkerson J.b · Beyer R.P.b · Farin F.M.b
Departments of aPediatrics and bEnvironmental and Occupational Health Sciences, University of Washington, Seattle, Wash., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 06, 2006
Accepted: December 23, 2006
Published online: October 25, 2007
Issue release date: May 2008

Number of Print Pages: 12
Number of Figures: 6
Number of Tables: 2

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE

Abstract

To identify neuroprotective changes in gene expression, we developed a neonatal mouse model of moderate to severe oxidative brain injury and hypothesized that recombinant erythropoietin (rEpo) would decrease the expression of proapoptotic and proinflammatory genes 24 and 48 h, respectively, after injury and increase the expression of neurogenic and angiogenic genes 168 h after injury. Postnatal day 10 BALB-c mice underwent sham surgery or right common carotid artery occlusion followed by alternating hypoxia and hyperoxia and were then treated with rEpo (5,000 U/kg s.c.) or saline (vehicle) daily for up to three doses. At death, gross brain injury was assessed, then hippocampus, cortex, and thalamus were isolated for RNA or protein extraction. Microarray analysis, real-time polymerase chain reaction, and Bio-Plex® suspension array system validation were performed. rEpo decreased both incidence and severity of brain injury (median injury score 3 vs. 0, p < 0.0001) and reduced the injury-induced increases in interleukin-1α and interleukin-6 gene expression (p < 0.001), with corresponding effects on protein translation. Similarly, the expression of caspase-1, caspase-4, and caspase-6 and of p53 was increased by brain injury at 24 h, but mitigated by rEpo (p < 0.01). The interleukin-10 expression was higher in the rEpo-treated animals. Apoptotic and proinflammatory gene expression persisted for 168 h. There was no increase in angiogenic gene expression at the time points studied.

© 2007 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 06, 2006
Accepted: December 23, 2006
Published online: October 25, 2007
Issue release date: May 2008

Number of Print Pages: 12
Number of Figures: 6
Number of Tables: 2

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE


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