Elucidation of the mechanism of rupture of intracranial aneurysm

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17929
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Miyata Haruka 滋賀医科大学, 医学部, 客員助教 (40869749)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: intracranial aneurysm / rupture

Outline of Final Research Achievements

Comprehensive gene expression analysis of the wall of intracranial aneurysms in model animals suggested the involvement of neutrophils in aneurysmal rupture. Spontaneous rupture of intracranial aneurysms was also significantly increased when neutrophil infiltration of the lesion was increased by G-CSF administration to the model animals. In ruptured aneurysm specimens, neutrophil infiltration was predominantly near the vasa vasorum of the wall, and in vivo detection of tissue hypoxia using Hypoxyprobe confirmed the presence of hypoxia in the outer membrane of cerebral aneurysms. Immunostaining showed the expression of FGF2 and VEGF in the same region. We hypothesized that hypoxic stimulation of the aneurysmal adventitia induces FGF2 and VEGF, which in turn induce vasa vasorum growth in the adventitia and rupture of the infiltrated neutrophils.

Free Research Field

脳動脈瘤

Academic Significance and Societal Importance of the Research Achievements

脳動脈瘤の破裂機序はこれまでほぼ解明されておらず、未破裂脳動脈瘤に対しての治療介入は外科治療しか選択肢が存在せず、内科治療の創出がunmet medical needとなっている。一方、破裂機序が解明されれば、脳動脈瘤破裂予防に対する薬物治療を創出しうる可能性がある。本研究で明らかになった好中球などの炎症を脳動脈瘤壁局所で制御できれば、脳動脈瘤破裂を予防できる可能性があり、社会的意義があるものと考えられる。