Development of novel treatment and prognostic prediction for acute brain injury after aneurysmal subarachnoid hemorrhage.

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16566
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Yokohama City University
• Principal Investigator: Takase Hajime 横浜市立大学, 医学研究科, 客員研究員 (00549975)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: くも膜下出血 / 急性期脳損傷 / 分子メカニズム / 血管内皮 / 神経炎症 / ミクログリア / cell-cell interaction / translational study

Outline of Final Research Achievements

We investigated the role of soluble vascular-endothelial (sVE) cadherin in aneurysmal subarachnoid hemorrhage (aSAH) that the inflammatory mechanism is strongly associated with the pathophysiology. The clinical part of our reverse-translational study demonstrated that CSF level of sVE-cadherin was negatively correlated with clinical outcome of aSAH patients. Additionally, the experimental part showed that sVE-cadherin activated an inflammatory cascade in microglia. These findings support the existence of a novel pathway by which sVE-cadherin, released from injured endothelium after SAH, can shift microglia into a more proinflammatory phenotype and contribute to neuroinflammation and poor outcome in SAH.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

本研究において、くも膜下出血における血管内皮細胞由来分子ーミクログリアの新たなcell-cell interactionと、新たな神経炎症分子メカニズムの存在が示唆された。血管内皮の代謝分子VE-cadherinが、血液脳関門の恒常性維持という本来の役割にとどまらず、中枢神経系の炎症において新たな生物学的な機能を有することを示した点で、学術的意義も大きいと考えられる。これらの知見を他の中枢神経疾患に応用することで、新たな研究展開が可能であり、将来の治療開発を通して世界の社会福祉に大きく貢献できる可能性がある。