• P Zhang, W Li, L Li, N Wang, X Li, M Gao, J Zheng, S Lei, X Chen, H Lu, and Y Liu.
• Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, #157 West 5 road, Xi'an, Shaanxi 710004, China. zhpbo@mail.xjtu.edu.cn
• Neuroscience. 2012 Jan 10;201:297-306.

AbstractEdaravone 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 1α (HIF-1α), 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-1α as well as VEGF protein levels in the ischemic ipsilateral SVZ (P<0.05). These findings indicate that administration with edaravone, via repressing HIF-1α signaling pathway, inhibits SVZ neurogenesis in rats after cerebral ischemia-reperfusion injury.Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

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