| Title |
Artesunate Protected Blood–Brain Barrier via Sphingosine 1 Phosphate Receptor 1/Phosphatidylinositol 3 Kinase Pathway After Subarachnoid Hemorrhage in Rats
|
|---|---|
| Published in |
Molecular Neurobiology, January 2016
|
| DOI | 10.1007/s12035-016-9732-6 |
| Pubmed ID | |
| Authors |
Shilun Zuo, Hongfei Ge, Qiang Li, Xuan Zhang, Rong Hu, Shengli Hu, Xin Liu, John H. Zhang, Yujie Chen, Hua 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 expression of Claudin-3 and Claudin-5 after SAH in rats. These effects were eliminated by S1P1 siRNA, VPC23019, and wortmannin. This study revealed that artesunate could preserve blood-brain barrier integrity and improve neurological outcome after SAH, possibly through activating S1P1, enhancing phosphatidylinositol 3-kinase activation, stabilizing β-catenin via GSK-3β inhibition, and then effectively raising the expression of Claudin-3 and Claudin-5. Therefore, artesunate may be favorable for the blood-brain barrier (BBB) protection after SAH and become a potential candidate for the treatment of SAH patients. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 30 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 30% |
| Student > Master | 5 | 17% |
| Student > Doctoral Student | 3 | 10% |
| Student > Bachelor | 3 | 10% |
| Researcher | 2 | 7% |
| Other | 2 | 7% |
| Unknown | 6 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 27% |
| Neuroscience | 5 | 17% |
| Biochemistry, Genetics and Molecular Biology | 4 | 13% |
| Agricultural and Biological Sciences | 2 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 3 | 10% |
| Unknown | 7 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 January 2016.
All research outputs
#14,246,461
of 22,842,950 outputs
Outputs from Molecular Neurobiology
#1,820
of 3,460 outputs
Outputs of similar age
#207,872
of 396,721 outputs
Outputs of similar age from Molecular Neurobiology
#79
of 183 outputs
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