Pre- and posttreatment with edaravone protects CA1 hippocampus and enhances neurogenesis in the subgranular zone of dentate gyrus after transient global cerebral ischemia in rats.
Edaravone is clinically used for treatment of patients with acute cerebral infarction. However, the effect of double application of edaravone on neurogenesis in the hippocampus following ischemia remains unknown. In the present study, we explored whether pre- and posttreatment of edaravone had any effect on neural stem/progenitor cells (NSPCs) in the subgranular zone of hippocampus in a rat model of transient global cerebral ischemia and elucidated the potential mechanism of its effects. Male Sprague-Dawley rats were divided into three groups: sham-operated (n = 15), control (n = 15), and edaravone-treated (n = 15) groups. Newly generated cells were labeled by 5-bromo-2-deoxyuridine. Immunohistochemistry was used to detect neurogenesis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling was used to detect cell apoptosis. Reactive oxygen species (ROS) were detected by 2,7-dichlorofluorescien diacetate assay in NSPCs in vitro. Hypoxia-inducible factor-1α (HIF-1α) and cleaved caspase-3 proteins were quantified by western blot analysis. Treatment with edaravone significantly increased the number of NSPCs and newly generated neurons in the subgranular zone (p < .05). Treatment with edaravone also decreased apoptosis of NSPCs (p < .01). Furthermore, treatment with edaravone significantly decreased ROS generation and inhibited HIF-1α and cleaved caspase-3 protein expressions. These findings indicate that pre- and posttreatment with edaravone enhances neurogenesis by protecting NSPCs from apoptosis in the hippocampus, which is probably mediated by decreasing ROS generation and inhibiting protein expressions of HIF-1α and cleaved caspase-3 after cerebral ischemia.
Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, China Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Shan
S
Lei
Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, China zhpbo@mail.xjtu.edu.cn.
Pengbo
P
Zhang
Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, China Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Weisong
W
Li
Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, China Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Ming
M
Gao
Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Xijing
X
He
Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, China Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Juan
J
Zheng
Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, China Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Xu
X
Li
Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, China Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Xiao
X
Wang
Department of Anesthesiology, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Ning
N
Wang
Department of Anatomy, Xi'an Medical University, Xi'an, China.
Junfeng
J
Zhang
Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Cunfang
C
Qi
Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Haixia
H
Lu
Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Xinlin
X
Chen
Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University School of Medicine, Xi'an, China.
Yong
Y
Liu
D000818:Animals; D000831:Animals, Newborn; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000187:drug effects*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000860:Hypoxia / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species
D000089622:Doublecortin Domain Proteins; D016166:Free Radical Scavengers; D005904:Glial Fibrillary Acidic Protein; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D017382:Reactive Oxygen Species; D000077553:Edaravone; D000983:Antipyrine
cerebral ischemia; edaravone; neural stem/progenitor cells; neurogenesis; neuroprotection; reactive oxygen species