Artesunate Protected Blood–Brain Barrier via Sphingosine 1 Phosphate Receptor 1/Phosphatidylinositol 3 Kinase Pathway After Subarachnoid Hemorrhage in Rats
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 hundre...
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| Veröffentlicht in: | Molecular neurobiology 2017-03, Vol.54 (2), p.1213-1228 |
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| creator | Zuo, Shilun Ge, Hongfei Li, Qiang Zhang, Xuan Hu, Rong Hu, Shengli Liu, Xin Zhang, John H. Chen, Yujie Feng, Hua |
| description | 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 S1P
1
, 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. |
| doi_str_mv | 10.1007/s12035-016-9732-6 |
| format | Article |
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1
, 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.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-016-9732-6</identifier><identifier>PMID: 26820677</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Artemisinins - pharmacology ; Artemisinins - therapeutic use ; Biomedical and Life Sciences ; Biomedicine ; Blood-brain barrier ; Blood-Brain Barrier - drug effects ; Blood-Brain Barrier - metabolism ; Blood-Brain Barrier - pathology ; Cell Biology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Hemorrhage ; Kinases ; Male ; Neurobiology ; Neurology ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; Neurosciences ; Phosphatidylinositol 3-Kinase - metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Lysosphingolipid - metabolism ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Subarachnoid Hemorrhage - metabolism ; Subarachnoid Hemorrhage - pathology ; Subarachnoid Hemorrhage - prevention & control</subject><ispartof>Molecular neurobiology, 2017-03, Vol.54 (2), p.1213-1228</ispartof><rights>Springer Science+Business Media New York 2016</rights><rights>Molecular Neurobiology is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-91a646bc0a7ccb4c16a591e4e0d11b937a67a89ad60e94580a52c1f9dfd136f63</citedby><cites>FETCH-LOGICAL-c471t-91a646bc0a7ccb4c16a591e4e0d11b937a67a89ad60e94580a52c1f9dfd136f63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-016-9732-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-016-9732-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27926,27927,41490,42559,51321</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26820677$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zuo, Shilun</creatorcontrib><creatorcontrib>Ge, Hongfei</creatorcontrib><creatorcontrib>Li, Qiang</creatorcontrib><creatorcontrib>Zhang, Xuan</creatorcontrib><creatorcontrib>Hu, Rong</creatorcontrib><creatorcontrib>Hu, Shengli</creatorcontrib><creatorcontrib>Liu, Xin</creatorcontrib><creatorcontrib>Zhang, John H.</creatorcontrib><creatorcontrib>Chen, Yujie</creatorcontrib><creatorcontrib>Feng, Hua</creatorcontrib><title>Artesunate Protected Blood–Brain Barrier via Sphingosine 1 Phosphate Receptor 1/Phosphatidylinositol 3 Kinase Pathway After Subarachnoid Hemorrhage in Rats</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>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 S1P
1
, 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.</description><subject>Animals</subject><subject>Artemisinins - pharmacology</subject><subject>Artemisinins - therapeutic use</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Blood-Brain Barrier - pathology</subject><subject>Cell Biology</subject><subject>Cells, Cultured</subject><subject>Dose-Response Relationship, Drug</subject><subject>Hemorrhage</subject><subject>Kinases</subject><subject>Male</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Neurosciences</subject><subject>Phosphatidylinositol 3-Kinase - metabolism</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Lysosphingolipid - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Subarachnoid Hemorrhage - metabolism</subject><subject>Subarachnoid Hemorrhage - pathology</subject><subject>Subarachnoid Hemorrhage - prevention & control</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkcFu1DAURSMEokPhA9ggS2zYhPo5sZ0sZyqgiEpULayjF8eZuMrYwXaKZtd_6Jqf40twNC1CSEisLNnn3fusk2Uvgb4FSuVJAEYLnlMQeS0LlotH2Qo4r3OAij3OVrSqi1yKsjrKnoVwTSljQOXT7IiJilEh5Sr7sfZRh9li1OTCu6hV1B3ZjM51P2_vNh6NJRv03mhPbgySq2kwduuCsZoAuRhcmIZl9lIrPUXnCZw8XJpuPxqb0OhGUpBPxmJIJRiH77gn6z6myKu5RY9qsM505EzvnPcDbjVJrZcYw_PsSY9j0C_uz-Ps6_t3X07P8vPPHz6ers9zVUqIeQ0oStEqilKptlQgkNegS007gLYuJAqJVY2doLoueUWRMwV93fUdFKIXxXH25pA7efdt1iE2OxOUHke02s2hgUrKitOC8f9AmRC8ZIIl9PVf6LWbvU0fSZSoeMkBlkA4UMq7ELzum8mbHfp9A7RZNDcHzU3S3Cyam2XfV_fJc7vT3e-JB68JYAcgpCe71f6P6n-m_gKBNLS5</recordid><startdate>20170301</startdate><enddate>20170301</enddate><creator>Zuo, Shilun</creator><creator>Ge, Hongfei</creator><creator>Li, Qiang</creator><creator>Zhang, Xuan</creator><creator>Hu, Rong</creator><creator>Hu, Shengli</creator><creator>Liu, Xin</creator><creator>Zhang, John H.</creator><creator>Chen, Yujie</creator><creator>Feng, Hua</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QR</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20170301</creationdate><title>Artesunate Protected Blood–Brain Barrier via Sphingosine 1 Phosphate Receptor 1/Phosphatidylinositol 3 Kinase Pathway After Subarachnoid Hemorrhage in Rats</title><author>Zuo, Shilun ; Ge, Hongfei ; Li, Qiang ; Zhang, Xuan ; Hu, Rong ; Hu, Shengli ; Liu, Xin ; Zhang, John H. ; Chen, Yujie ; Feng, Hua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-91a646bc0a7ccb4c16a591e4e0d11b937a67a89ad60e94580a52c1f9dfd136f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Artemisinins - pharmacology</topic><topic>Artemisinins - therapeutic use</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Blood-Brain Barrier - pathology</topic><topic>Cell Biology</topic><topic>Cells, Cultured</topic><topic>Dose-Response Relationship, Drug</topic><topic>Hemorrhage</topic><topic>Kinases</topic><topic>Male</topic><topic>Neurobiology</topic><topic>Neurology</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Neurosciences</topic><topic>Phosphatidylinositol 3-Kinase - metabolism</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Lysosphingolipid - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>Subarachnoid Hemorrhage - metabolism</topic><topic>Subarachnoid Hemorrhage - pathology</topic><topic>Subarachnoid Hemorrhage - prevention & control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zuo, Shilun</creatorcontrib><creatorcontrib>Ge, Hongfei</creatorcontrib><creatorcontrib>Li, Qiang</creatorcontrib><creatorcontrib>Zhang, Xuan</creatorcontrib><creatorcontrib>Hu, Rong</creatorcontrib><creatorcontrib>Hu, Shengli</creatorcontrib><creatorcontrib>Liu, Xin</creatorcontrib><creatorcontrib>Zhang, John H.</creatorcontrib><creatorcontrib>Chen, Yujie</creatorcontrib><creatorcontrib>Feng, Hua</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Psychology Database (ProQuest)</collection><collection>ProQuest Science Journals</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zuo, Shilun</au><au>Ge, Hongfei</au><au>Li, Qiang</au><au>Zhang, Xuan</au><au>Hu, Rong</au><au>Hu, Shengli</au><au>Liu, Xin</au><au>Zhang, John H.</au><au>Chen, Yujie</au><au>Feng, Hua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Artesunate Protected Blood–Brain Barrier via Sphingosine 1 Phosphate Receptor 1/Phosphatidylinositol 3 Kinase Pathway After Subarachnoid Hemorrhage in Rats</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2017-03-01</date><risdate>2017</risdate><volume>54</volume><issue>2</issue><spage>1213</spage><epage>1228</epage><pages>1213-1228</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><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 S1P
1
, 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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>26820677</pmid><doi>10.1007/s12035-016-9732-6</doi><tpages>16</tpages></addata></record> |
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| ispartof | Molecular neurobiology, 2017-03, Vol.54 (2), p.1213-1228 |
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| subjects | Animals Artemisinins - pharmacology Artemisinins - therapeutic use Biomedical and Life Sciences Biomedicine Blood-brain barrier Blood-Brain Barrier - drug effects Blood-Brain Barrier - metabolism Blood-Brain Barrier - pathology Cell Biology Cells, Cultured Dose-Response Relationship, Drug Hemorrhage Kinases Male Neurobiology Neurology Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Neurosciences Phosphatidylinositol 3-Kinase - metabolism Random Allocation Rats Rats, Sprague-Dawley Receptors, Lysosphingolipid - metabolism Signal Transduction - drug effects Signal Transduction - physiology Subarachnoid Hemorrhage - metabolism Subarachnoid Hemorrhage - pathology Subarachnoid Hemorrhage - prevention & control |
| title | Artesunate Protected Blood–Brain Barrier via Sphingosine 1 Phosphate Receptor 1/Phosphatidylinositol 3 Kinase Pathway After Subarachnoid Hemorrhage in Rats |
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