Targeting Blood-Brain Barrier Protection to Develop Therapeutic Agents for Central Nervous System Diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08973
• 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: Nagasaki University
• Principal Investigator: Izumo Tsuyoshi 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (40343347)
• Co-Investigator(Kenkyū-buntansha): 諸藤 陽一 長崎大学, 病院(医学系), 講師 (40437869) ; 藤本 隆史 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (00712085)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 血液脳関門 / 脳梗塞 / 転移性脳腫瘍 / ドラッグリポジショニング

Outline of Final Research Achievements

In this study, we used multiple co-cultured in vitro BBB models combining all cells of the blood-brain barrier (BBB), such as brain capillary endothelial cells, pericytes, and astrocytes, to create pathological models (ischemia, inflammation, cancer brain metastasis), and developed a perfusion-type 3D BBB model to investigate cell-cell interactions in the neurovascular unit. We also developed a perfused 3D BBB model and investigated cell-cell interactions in the neurovascular unit. In addition, we investigated the effects of drugs currently used in clinical practice on the BBB and their mechanisms of action. By elucidating these mechanisms, we have been conducting research with the aim of developing therapeutic agents for central nervous system diseases and, ultimately, a completely new concept of drug discovery, "BBB-protective drugs".

Free Research Field

脳科学

Academic Significance and Societal Importance of the Research Achievements

BBBの機能構築には基本構成単位である脳毛細血管内皮細胞、ペリサイト、及びアストロサイト間のクロストークが不可欠であり、このクロストーク不全が中枢神経疾患の発生に繋がることが明らかとなりつつある。本研究では、転移性脳腫瘍・造影剤脳症そして脳血管攣縮治療薬のBBBにおける作用機序とクロストークについて明らかにしてきた。BBB機能の制御またそのメカニズムを解明することにより、中枢神経疾患全般における、更なる病態解明、治療薬の発見と開発につながると考える。