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Pinocembrin Protects Blood-Brain Barrier Function and Expands the Therapeutic Time Window for Tissue-Type Plasminogen Activator Treatment in a Rat Thromboembolic Stroke Model
المؤلفون المشاركون
Du, Guan-Hua
Li, Li
Ma, YinZhong
Kong, LingLei
Zhu, ZhiMei
Zhang, Wen
Song, JunKe
Chang, Junlei
المصدر
العدد
المجلد 2018، العدد 2018 (31 ديسمبر/كانون الأول 2018)، ص ص. 1-13، 13ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2018-04-22
دولة النشر
مصر
عدد الصفحات
13
التخصصات الرئيسية
الملخص 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.
نمط استشهاد جمعية علماء النفس الأمريكية (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
نمط استشهاد الجمعية الأمريكية للغات الحديثة (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
نمط استشهاد الجمعية الطبية الأمريكية (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
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1129398
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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