2022 Fiscal Year Final Research Report
Novel interventional therapy improves collateral development and outcome after stroke
Project/Area Number |
20K09366
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56010:Neurosurgery-related
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Miki Kazunori 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (00536823)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 脳動脈新生 / 脳血管障害 / arteriogenesis / スフィンゴシン1リン酸受容体1 / microRNA |
Outline of Final Research Achievements |
Collateral glows after acute ischemic stroke are triggered by shear stress, and sphingosine-1-phosphate receptor 1 (S1PR1) on endothelial cells was reported to sense shear stress and transduce its signaling pathways. We investigated the effect of an S1P1-selective agonist (SEW2871) on leptomeningeal collateral arteries in acute stroke model. Neurological functions, leptomeningeal arteries, and infarct volume were compared after treatment. S1P1 expression in endothelial cells was increased after CCAO and pMCAO. The number of leptomeningeal collateral arteries was significantly increased, and neurological outcome improved. Endothelial nitric oxide synthase (eNOS) phosphorylation and the expression of tight junction proteins was increased in the SEW2871 group. S1PR1 selective agonist has a role in promoting collateral growth and preventing of ischemic damage and neurological dysfunction after subsequent stroke in patients with intracranial major artery stenosis or occlusion.
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Free Research Field |
脳血管障害
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Academic Significance and Societal Importance of the Research Achievements |
脳梗塞治療として再開通療法と同時に、脳血流の低下を防ぎ、いかに梗塞に陥らせないかという治療戦略は重要であり、多くの脳梗塞症例に適応しうる。実際に我々は脳表の動脈新生の発達したヒト脳梗塞でが梗塞体積が少なく、機能予後が良好であること確認してきた。成体脳であっても脳梗塞後に新たな血管が形成される現象が認められ、特に血管内皮細胞だけでなく平滑筋、基底膜よりなる大口径の機能動脈のリモデリングを意味するArteriogenesis (動脈新生)が制御できれば、脳主幹動脈閉塞の場合に側副血行路を介した脳血流の保持が可能となるため動脈新生の発達を促す方法の開発が期待されているが、未だ開発されていない。
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