Neutrophil extracellular traps attribute to cerebral vascular disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16562
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: The University of Tokushima
• Principal Investigator: KORAI Masaaki 徳島大学, 大学院医歯薬学研究部(医学域), 徳島大学専門研究員 (60794013)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: NETs / 脳血管障害 / PAD4 / 炎症性変化 / 脳動脈瘤

Outline of Final Research Achievements

We have demonstrated the relationships between the vascular inflammation and the ruptured intracranial aneurysms (IAs). Here, we examined the role of NETs in IAs rupture to test out hypothesis that the presence of neutrophil extracellular traps (NETs) may promote the rupture of IAs. Other study reported that granulocyte-specific knockout of peptidyl arginine deiminase 4 (PAD4) reduced the rate of aneurysm rupture. We found that pharmacological blockade of the NET formation by Cl-amidine (hydrochloride); an irreversible pan-PAD inhibitor reduced the rate of aneurysm rupture and decreased mRNA expression of pro-inflammatory cytokines These findings suggest that NETs promote the rupture of IAs and that the inhibition of PAD4 or resolution of already-formed NETs by deoxyribonuclease may represent a potential therapeutic strategy for preventing aneurysmal rupture. We also confirmed the presence of NETs in the other cerebral vascular diseases.

Free Research Field

脳血管障害

Academic Significance and Societal Importance of the Research Achievements

くも膜下出血の原因となる脳動脈瘤破裂などの脳血管障害の成因には不明の点が多いが、重篤な予後を呈する場合もあり、本人のみならず社会的な損失も大きい。今回、脳動脈瘤破裂など重篤な脳血管障害とNETs発現との関連性を調べ、NETs形成を活性化するメカニズムやNETs制御による脳血管障害への影響を明らかにできれば、NETs発現を指標として発症予防だけでなく、治療標的としての創薬の可能性もあるため、高齢化社会での社会的意義は高いと考えられる。