Artesunate Protected Blood-Brain Barrier via Sphingosine 1 Phosphate Receptor 1/Phosphatidylinositol 3 Kinase Pathway After Subarachnoid Hemorrhage in Rats

Molecular Neurobiology
Shilun ZuoHua Feng

Abstract

Blood-brain barrier preservation plays an important role in attenuating vasogenic brain edema after subarachnoid hemorrhage (SAH). This study was designed to investigate the protective effect and mechanism of artesunate, a traditional anti-malaria drug, on blood-brain barrier after SAH. Three hundred and seventy-seven (377) male Sprague-Dawley rats were subjected to endovascular perforation model for SAH. The rats received artesunate alone or in combination with Sphingosine-1-phosphate receptor-1 (S1P1) small interfering RNA (siRNA), antagonist VPC23019, or phosphatidylinositol 3-kinase inhibitor wortmannin after SAH. Modified Garcia score, SAH grades, brain water content, Evans blue leakage, transmission electron microscope, immunohistochemistry staining, Western blot, and cultured endothelial cells were used to investigate the optimum concentration and the therapeutic mechanism of artesunate. We found that artesunate (200 mg/kg) could do better in raising modified Garcia score, reducing brain water content and Evans blue leakage than other groups after SAH. Moreover, artesunate elevated S1P1 expression, enhanced phosphatidylinositol 3-kinase activation, lowered GSK-3β activation, stabilized β-catenin, and improved the express...Continue Reading

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Citations

Feb 26, 2019·Neural Regeneration Research·Hideki Kanamaru, Hidenori Suzuki
Jun 29, 2017·Pharmacological Reviews·Anna CooperAndrea J Vernall
Apr 16, 2020·Cell Communication and Signaling : CCS·Yunxiang ZhouJianmin Zhang
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Aug 1, 2020·Frontiers in Neurology·Gen LiGuobiao Liang
Oct 20, 2020·Frontiers in Physiology·Romain MenetAyman ElAli
Dec 19, 2020·Translational Neuroscience·Zhike ZhouQinghua Li

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Methods Mentioned

BETA
Fluorescence
protein extraction
nuclear translocation

Software Mentioned

Quantity One
SPSS

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