title: Treatment with edaravone attenuates ischemic brain injury and inhibits neurogenesis in the subventricular zone of adult rats after focal cerebral ischemia and reperfusion injury.
abstract: 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 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.
authors: 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
authors: P
authors: P
authors: Zhang
authors: W
authors: W
authors: Li
authors: L
authors: L
authors: Li
authors: N
authors: N
authors: Wang
authors: X
authors: X
authors: Li
authors: M
authors: M
authors: Gao
authors: J
authors: J
authors: Zheng
authors: S
authors: S
authors: Lei
authors: X
authors: X
authors: Chen
authors: H
authors: H
authors: Lu
authors: Y
authors: Y
authors: Liu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001973:Bromodeoxyuridine / Q000378:metabolism; D002544:Cerebral Infarction / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000209:etiology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D016166:Free Radical Scavengers; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D001973:Bromodeoxyuridine; D000077553:Edaravone; D000983:Antipyrine