期刊
NEUROSCIENCE
卷 391, 期 -, 页码 60-72出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2018.09.006
关键词
2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-beta-D-pyranoside; therapeutic time window; glucose metabolism; positron emission tomography (PET); glucose transporter; ischemic stroke
资金
- National Key Basic Research Program of China (973 program) [2014CB542203]
- National Natural Science Foundation of China [81401094, 81501058]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Jiangsu Provincial Key Medical Center
2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-beta-D-pyranoside (salidroside analog-4g, SalA-4g), has shown neuroprotective prospects for the treatment of ischemic stroke. However, the dose-response and time window study for SalA-4g, and the mechanism of SalA-4g-mediated neuroprotection remain unclear. Here, we systematically investigated the therapeutic time window and dosage of SalA-4g in permanent focal cerebral ischemia in rats. SalA-4g dose-dependently improved stroke outcome. Either pre-treatment or post-treatment of SalA-4g exhibited notable neuroprotection, and maintained for up to 6 h after ischemia onset. Moreover, significant neurological functional recovery was found after SalA-4g administration in long-term functional assays. Further studies suggested that SalA-4g ameliorated neuronal cell death, elevated local glucose metabolism and enhanced the expression level of glucose transporter 1 and 3 in the ipsilateral cortex and striatum. We suggest that data of this study are critical in exploring the clinical application prospects of SalA-4g for the treatment of ischemic stroke. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
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