Analysis for signaling mechanisms linking inflammatory vessel-associated microglia and hypertensive cerebral small vessel disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16500
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Koizumi Takashi 京都府立医科大学, 医学(系)研究科(研究院), 助教 (50867455)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 高血圧性脳小血管病 / ミクログリア / 神経炎症

Outline of Final Research Achievements

This study aimed to elucidate the involvement of vessel-associated microglia in cerebral small vessel disease(cSVD) caused by hypertension. First, using a chronic hypertension model rat, we comprehensively analyzed genes that are altered during the process of blood pressure elevation. We chose a candidate gene X among them, which could attract microglia to the perivascular area. Next, the distribution of molecule X and its receptor X were evaluated immunohistochemically to confirm that the expression of receptor X increased over time on microglia and that molecule X is involved in microglial migration using cultured tissue in a chemotaxis assay. The results of the present study indicated microglia could migrate toward vessels via Molecule X. For future studies, we do further administrate the inhibitor of Moleule X to rat models to confirm that vascular injuries could be suppressed.

Free Research Field

脳神経学

Academic Significance and Societal Importance of the Research Achievements

高血圧性脳小血管病は血管性認知症を引き起こし得る。高齢化社会における認知症発症予防は喫緊の課題であり、高血圧性脳小血管病は予防可能な疾患となりうる。しかしながら、その発症メカニズムには不明な点も多く、単純に降圧治療を行っただけでは進行が予防できない事がある。これまでの報告並びに我々の研究結果から、高血圧性脳小血管障害には神経炎症が関わっている事が示唆される。さらに本研究結果から分子Xが神経炎症を引き起こすきっかけである可能性がある。引き続き分子Xの関与を詳細に調べることで高血圧性脳小血管病発症予防、ひいては認知症予防のための新たな治療ストラテジーを提供できることが期待できる。