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Neuroprotective effects of Ginkgo biloba extract and Ginkgolide B against oxygen–glucose deprivation/reoxygenation and glucose injury in a new in vitro multicellular network model |
Xiaohan Yang1,2,3,4, Tiezheng Zheng1,2,3,4, Hao Hong4, Nan Cai4, Xiaofeng Zhou4, Changkai Sun1,2,3,4(), Liying Wu5, Shuhong Liu5, Yongqi Zhao5, Lingling Zhu5, Ming Fan5(), Xuezhong Zhou6(), Fengxie Jin7 |
1. Department of Biomedical Engineering, Faculty of Electronic Information and Electrical Engineering, Dalian University of Technology, Dalian 116024, China 2. Research Center for the Control Engineering of Translational Precision Medicine, Dalian University of Technology, Dalian 116024, China 3. State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China 4. Liaoning Provincial Key Laboratory of Cerebral Diseases, Institute for Brain Disorders, Dalian Medical University, Dalian 116044, China 5. Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing 100850, China 6. School of Computer and Information Technology and Beijing Key Lab of Traffic Data Analysis and Mining, Beijing Jiaotong University, Beijing 100044, China 7. College of Biotechnology, Dalian Polytechnic University, Dalian 116034, China |
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Abstract Acute ischemic stroke (AIS), as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba extract (GBE) against several cerebral diseases have been reported in previous studies, but the underlying mechanisms of action are still unclear. Using a novel in vitro rat cortical capillary endothelial cell-astrocyte-neuron network model, we investigated the neuroprotective effects of GBE and one of its important constituents, Ginkgolide B (GB), against oxygen–glucose deprivation/reoxygenation and glucose (OGD/R) injury. In this model, rat cortical capillary endothelial cells, astrocytes, and neurons were cocultured so that they could be synchronously observed in the same system. Pretreatment with GBE or GB increased the neuron cell viability, ameliorated cell injury, and inhibited the cell apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury. Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical resistance of capillary endothelial monolayers, reduced the endothelial permeability coefficients for sodium fluorescein (Na-F), and increased the expression levels of tight junction proteins, namely, ZO-1 and occludin, in endothelial cells. Results demonstrated the preventive effects of GBE on neuronal cell death and enhancement of the function of brain capillary endothelial monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective neuroprotective agent for AIS/reperfusion, with GB as one of its significant constituents.
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Keywords
acute ischemic stroke
Ginkgo biloba extract
Ginkgolide B
network model
neuroprotection
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Corresponding Author(s):
Changkai Sun,Ming Fan,Xuezhong Zhou
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Just Accepted Date: 18 July 2017
Online First Date: 08 November 2017
Issue Date: 04 May 2018
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