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
YinZhong MaGuanHua Du

Abstract

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 mode...Continue Reading

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Citations

Feb 26, 2019·Neural Regeneration Research·Ling-Yi LiaoQiang Gao
Mar 10, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Nur Shafika Mohd Sairazi, K N S Sirajudeen
Dec 10, 2019·Oxidative Medicine and Cellular Longevity·Solomon Habtemariam
Jun 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xiaoling ShenZhihong Yang
Oct 31, 2020·Cellular and Molecular Neurobiology·Chengli LiuWei Wang
Nov 12, 2020·Medicinal Research Reviews·Cinthia C S Menezes da SilveiraCristiane S F Maia
Nov 13, 2020·Journal of Primary Care & Community Health·Rowaida Elyamani, Hamed Hammoud
May 9, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Nannan LiuGuanhua Du
May 20, 2021·Oxidative Medicine and Cellular Longevity·Hui XuMingfu Wang
May 11, 2020·Current Hypertension Reviews·Alejandro F do PradoCésar A Meschiari

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