Sema3E/PlexinD1 inhibition is a therapeutic strategy for improving cerebral perfusion and restoring functional loss after stroke in aged rats
文献类型：期刊论文
| 作者 | Yue, Zhen-Yu9; Zhou, Yi-Fan1; Li, Peng-Cheng2; Wu, Jie-Hong1; Haslam, James Andrew3; Mao, Ling1; Xia, Yuan-Peng1; He, Quan-Wei1; Wang, Xu-Xia4; Lei, Hao4 |
| 刊名 | NEUROBIOLOGY OF AGING
 |
| 出版日期 | 2018-10-01 |
| 卷号 | 70页码:102-116 |
| 关键词 | Ischemic stroke Cerebral perfusion Functional neovascularization BBB integrity Endothelial cells Pericytes |
| ISSN号 | 0197-4580 |
| DOI | 10.1016/j.neurobiolaging.2018.06.003 |
| 英文摘要 | Brain tissue survival and functional recovery after ischemic stroke greatly depend on cerebral vessel perfusion and functional collateral circulation in the ischemic area. Semaphorin 3E (Sema3E), one of the class 3 secreted semaphorins, has been demonstrated to be a critical regulator in embryonic and postnatal vascular formation via binding to its receptor PlexinD1. However, whether Sema3E/PlexinD1 signaling is involved in poststroke neovascularization remains unknown. To determine the contribution of Sema3E/PlexinD1 signaling to poststroke recovery, aged rats (18 months) were subjected to a transient middle cerebral artery occlusion. We found that depletion of Sema3E/PlexinD1 signaling with lentivirus-mediated PlexinD1-specific-shRNA improves tissue survival and functional outcome. Sema3E/PlexinD1 inhibition not only increases cortical perfusion but also ameliorates blood-brain barrier damage, as determined by positron emission tomography and magnetic resonance imaging. Mechanistically, we demonstrated that Sema3E suppresses endothelial cell proliferation and angiogenic capacity. More importantly, Sema3E/PlexinD1 signaling inhibits recruitment of pericytes by decreasing production of platelet derived growth factor-BB in endothelial cells. Overall, our study revealed that inhibition of Sema3E/PlexinD1 signaling in the ischemic penumbra, which increases both endothelial angiogenic capacity and recruitment of pericytes, contributed to functional neovascularization and blood-brain barrier integrity in the aged rats. Our findings imply that Sema3E/PlexinD1 signaling is a novel therapeutic target for improving brain tissue survival and functional recovery after ischemic stroke. (C) 2018 Elsevier Inc. All rights reserved. |
| 资助项目 | National Natural Science Foundation of China[81601027] ; National Natural Science Foundation of China[81571119] ; National Natural Science Foundation of China[81571139] ; National Natural Science Foundation of China[81771249] ; National Natural Science Foundation of China[81400969] ; National Natural Science Foundation of China[81400970] ; National Natural Science Foundation of China[81301001] ; National Key Research and Development Program of China[2016YFC1300600] ; National Research Foundation for the Doctoral Program of Higher Education of China[20120142110068] ; New Century Excellent Talents in University[NCET-10-0406] |
| WOS研究方向 | Geriatrics & Gerontology ; Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000442879100012 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/5635]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Li, Ya-Nan; Hu, Bo |
| 作者单位 | 1.Huazhong Univ Sci & Technol, Union Hosp, Dept Neurol, Tongji Med Coll, Wuhan 430022, Hubei, Peoples R China 2.Huazhong Univ Sci & Technol, Union Hosp, Dept Ophthalmol, Tongji Med Coll, Wuhan, Hubei, Peoples R China 3.Swansea Univ, Swansea Coll Med, Singleton Pk, Swansea, W Glam, Wales 4.Chinese Acad Sci, Wuhan Inst Phys & Math, Wuhan Ctr Magnet Resonance, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan, Hubei, Peoples R China 5.Huazhong Univ Sci & Technol, Union Hosp, Dept Nucl Med, Tongji Med Coll, Wuhan, Hubei, Peoples R China 6.Med Coll Wisconsin, Dept Surg, Div Pediat Surg, Childrens Res Inst, 8700 W Wisconsin Ave, Milwaukee, WI 53226 USA 7.Med Coll Wisconsin, Dept Pathol, Childrens Res Inst, Div Pediat Pathol, Milwaukee, WI 53226 USA 8.Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA 9.Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Neurosci, Dept Neurol, New York, NY 10029 USA |
| 推荐引用方式 GB/T 7714 | Yue, Zhen-Yu,Zhou, Yi-Fan,Li, Peng-Cheng,et al. Sema3E/PlexinD1 inhibition is a therapeutic strategy for improving cerebral perfusion and restoring functional loss after stroke in aged rats[J]. NEUROBIOLOGY OF AGING,2018,70:102-116. |
| APA | Yue, Zhen-Yu.,Zhou, Yi-Fan.,Li, Peng-Cheng.,Wu, Jie-Hong.,Haslam, James Andrew.,...&Hu, Bo.(2018).Sema3E/PlexinD1 inhibition is a therapeutic strategy for improving cerebral perfusion and restoring functional loss after stroke in aged rats.NEUROBIOLOGY OF AGING,70,102-116. |
| MLA | Yue, Zhen-Yu,et al."Sema3E/PlexinD1 inhibition is a therapeutic strategy for improving cerebral perfusion and restoring functional loss after stroke in aged rats".NEUROBIOLOGY OF AGING 70(2018):102-116. |
入库方式： OAI收割
来源：武汉植物园
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。