Pinocembrin Protects Blood-Brain Barrier Function and Expands the Therapeutic Time Window for Tissue-Type Plasminogen Activator Treatment in a Rat Thromboembolic Stroke Model
Joint Authors
Du, Guan-Hua
Li, Li
Ma, YinZhong
Kong, LingLei
Zhu, ZhiMei
Zhang, Wen
Song, JunKe
Chang, Junlei
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-04-22
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
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-PA infusion-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 α (PDGFRα) 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.
American Psychological Association (APA)
Ma, YinZhong& Li, Li& Kong, LingLei& Zhu, ZhiMei& Zhang, Wen& Song, JunKe…[et al.]. 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،Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1129398
Modern Language Association (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 No. 2018 (2018), pp.1-13.
https://search.emarefa.net/detail/BIM-1129398
American Medical Association (AMA)
Ma, YinZhong& Li, Li& Kong, LingLei& Zhu, ZhiMei& Zhang, Wen& Song, JunKe…[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. Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1129398
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1129398