Journal
NEUROSCIENCE
Volume 201, Issue -, Pages 297-306Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2011.11.005
Keywords
neurogenesis; reactive oxygen species; hypoxia-inducible factor 1 alpha; cerebral ischemia; reperfusion injury
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Funding
- National Natural Science Foundation of China [30772081, 81071071]
- Program for New Century Excellent Talents in University [NCET-08-0436]
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Edaravone is a novel free radical scavenger that is clinically employed in patients with acute cerebral infarction. However, its effect on stroke-induced subventricular zone (SVZ) neurogenesis is largely unknown. In this study, we investigated the effect and underlying mechanism of edaravone administration on SVZ neurogenesis using a rat model of cerebral ischemia-reperfusion injury. Male Sprague-Dawley rats (200-250 g) were divided into sham operated (n=15), control (n=50), and edaravone-treated (n=50) groups. Rats in the control and edaravone-treated groups underwent 90 min of middle cerebral artery occlusion (MCAO) following reperfusion. Immediately and 12 h after MCAO, the rats received either normal saline (control group) or edaravone (edaravone-treated group) intraperitoneally. 5-bromo-2-deoxyuridine (BrdU) was used to label proliferating cells. Six, 12, and 24 hours after ischemia, reactive oxygen species (ROS) generation, hypoxia-inducible factor 1 alpha (HIF-1 alpha), and vascular endothelial growth factor (VEGF) protein levels in ischemic ipsilateral SVZ were determined. Immunohistochemistry staining for BrdU and doublecortin (DCX) was performed at 1, 4, and 7 days after ischemia. Treatment with edaravone not only mitigated cerebral infarct size (P<0.05) and neurological defects (P<0.05), but also decreased cell proliferation and neural progenitor cells in the ischemic ipsilateral SVZ (P<0.05). Additionally, edaravone reduced effectively ROS generation and HIF-1 alpha as well as VEGF protein levels in the ischemic ipsilateral SVZ (P<0.05). These findings indicate that administration with edaravone, via repressing HIF-1 alpha signaling pathway, inhibits SVZ neurogenesis in rats after cerebral ischemia-reperfusion injury. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
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