Fasudil,a Rho kinase inhibitor,drives mobilization of adult neural stem cells after hypoxia/reoxygenation injury in mice |
| |
| Authors: | Jing Ding Qin-Ying Li Jie-Zhong Yu Xin Wang Chang-Hai Sun Chuan-Zhen Lu Bao-Guo Xiao |
| |
| Institution: | 1. Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 12 Middle Wulumuqi Road, 200040, Shanghai, China;2. Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China;3. Institute of Brain Science, Shanxi Datong University, 037009, China;4. Department of R&D, Tianjin Chasesun Pharmaceutical Co., Ltd. Tianjin, China;1. Department of Neurosurgery, University of Giessen, Giessen, Germany;2. Department of Neurology, University of Goettingen, Goettingen, Germany;3. Institute of Surgical Research, University of Marburg, Marburg, Germany;4. Department of Neurology, University of Marburg, Marburg, Germany;1. Clinical Research Center and Department of Neurology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China;2. Department of Pharmacology & Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio;1. Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China;2. Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China;3. Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha 410013, China;1. Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan;2. Stroke Program, University of Michigan Medical School, Ann Arbor, Michigan;1. CAS Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China;2. Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100080, China;3. Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China;1. Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA;2. SCYNEXIS Inc., 3501 C Tricenter Boulevard, Durham, NC 27713, USA |
| |
| Abstract: | Rho kinase (ROCK) is important in fundamental processes of cell proliferation and survival. Blockade of ROCK promotes stem cell survival in vitro and axonal regeneration in vivo, exhibiting therapeutic potential such as spinal cord injuries and stroke. Here, we used the model of hypoxia/reoxygenation (H/R) injury to explore the possibility whether Fasudil, a ROCK inhibitor in clinical application for subarachnoid hemorrhage and stroke, mobilizes adult neural stem cells in vivo. Most interestingly, Fasudil triggers neurogenesis especially in the subventricular zone after H/R. The increase of Brdu+ cholinergic neurons was observed in striatum and forebrain cortex of Fasudil-treated mice after 30 days. Further observation demonstrates that both levels of granulocyte colony-stimulating factor (G-CSF) and astrocytes expressing G-CSF were elevated in mice treated with Fasudil, as compared to mice injected with saline. In vitro H/R model of cultured astrocytes, Fasudil promoted astrocytes to produce G-CSF in a dose-dependent manner. In addition, antibody neutralization and receptor blocking of the G-CSF pathway clearly demonstrate that Fasudil-induced neurogenesis was mediated partially through astrocyte-derived G-CSF. Our results indicate that Fasudil might represent a promising therapeutic perspective by mobilizating endogenous adult neural stem cells in the CNS. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
