Pinocembrin Protects Blood-Brain Barrier Function and Expands the Therapeutic Time Window for Tissue-Type Plasminogen Activator Treatment in a Rat Thromboembolic Stroke Model.
文献类型：期刊论文
| 作者 | Ma, YinZhong; Li, Li; Kong, LingLei; Zhu, ZhiMei; Zhang, Wen; Song, JunKe; Chang, Junlei; Du, GuanHua |
| 刊名 | BIOMED RESEARCH INTERNATIONAL
 |
| 出版日期 | 2018 |
| 文献子类 | 期刊论文 |
| 英文摘要 | Tissue-type plasminogen activator (t-PA) remains the only approved therapy for acute ischemic stroke but has a restrictive treatment time window of 4.5 hr. Prolonged ischemia causes blood-brain barrier (BBB) damage and increases the incidence of hemorrhagic transformation (HT) secondary to reperfusion. In this study, we sought to determine the effect of pinocembrin (PCB; a pleiotropic neuroprotective agent) on t-PA administration-induced BBB damage in a novel rat thromboembolic stroke model. By assessing the leakage of Evans blue into the ischemic hemisphere, we demonstrated that PCB pretreatment 5 min before t-PA administration significantly reduced BBB damage following 2 hr, 4 hr, 6 hr, and even 8 hr ischemia. Consistently, PCB pretreatment significantly decreased t-PAinfusion-resulting brain edema and infarction volume and improved the behavioral outcomes following 6 hr ischemia. Mechanistically, PCB pretreatment inhibited the activation of MMP-2 and MMP-9 and degradation of tight junction proteins (TJPs) occludin and claudin-5 in the ischemic hemisphere. Moreover, PCB pretreatment significantly reduced phosphorylation of platelet-derived growth factor receptor alpha (PDGFR alpha) as compared with t-PA alone. In an in vitro BBB model, PCB decreased transendothelial permeability upon hypoxia/aglycemia through inhibiting PDGF-CC secretion. In conclusion, we demonstrated that PCB pretreatment shortly before t-PA infusion significantly protects BBB function and improves neurological outcomes following prolonged ischemia beyond the regular 4.5 hr t-PA time window. PCB pretreatment may represent a novel means of increasing the safety and the therapeutic time window of t-PA following ischemic stroke. |
| URL标识 | 查看原文 |
| 语种 | 英语 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/14632]  |
| 专题 | 深圳先进技术研究院_医药所 |
| 推荐引用方式 GB/T 7714 | Ma, YinZhong,Li, Li,Kong, LingLei,et al. Pinocembrin Protects Blood-Brain Barrier Function and Expands the Therapeutic Time Window for Tissue-Type Plasminogen Activator Treatment in a Rat Thromboembolic Stroke Model.[J]. BIOMED RESEARCH INTERNATIONAL,2018. |
| APA | Ma, YinZhong.,Li, Li.,Kong, LingLei.,Zhu, ZhiMei.,Zhang, Wen.,...&Du, GuanHua.(2018).Pinocembrin Protects Blood-Brain Barrier Function and Expands the Therapeutic Time Window for Tissue-Type Plasminogen Activator Treatment in a Rat Thromboembolic Stroke Model..BIOMED RESEARCH INTERNATIONAL. |
| MLA | Ma, YinZhong,et al."Pinocembrin Protects Blood-Brain Barrier Function and Expands the Therapeutic Time Window for Tissue-Type Plasminogen Activator Treatment in a Rat Thromboembolic Stroke Model.".BIOMED RESEARCH INTERNATIONAL (2018). |
入库方式： OAI收割
来源：深圳先进技术研究院
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