Identification of therapeutic targets to prevent rupture of intracranial aneurysm.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09381
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: AOKI TOMOHIRO 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (40633144)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 脳動脈瘤 / 慢性炎症

Outline of Final Research Achievements

In the present study, we have picked up three candidates which may be involved in the pathogenesis of intracranial aneurysms, a major cause of subarachnoid hemorrhage, through previously acquired comprehensive gene expression profile data. We have then established the rat line deficient in each gene and subjected animals to the model of intracranial aneurysms. Also, the drug specifically inhibits the activity of identified target is applied to models and the effect of each drug have been examined. We have then successfully identified two factors as a novel one regulating the pathogenesis. In addition, we have identified the unique macrophage subtypes exclusively present in the growing lesions. We have also clarified some but crucial mechanisms underlying the rupture of the lesions; the induction of neovessels and the infiltration of neutrophils across them.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、脳動脈瘤という疾患を対象としつつも、多くの疾患に共通の病態制御基盤である慢性炎症局面の形成機構やその変容を制御する分子機構の一端を明らかとしたものである。その点で、生物学医学研究としての学術的意義を有する。また、取り扱う脳動脈瘤は破裂によりくも膜下出血を発症させる。くも膜下出血が、死亡率も後遺症率も高い疾患であるために、その主要な原因疾患である脳動脈瘤の増大やそれに引き続く破裂を制御誘導する機構を明らかとすることは、新規治療法の開発に資する。その点で、アンメットメディカルニースの克服に直結するために社会的意義も大きい。