Joint international research for developing new drugs in the cerebral vascular diseases by targeting RAGE signaling

2023 Fiscal Year Final Research Report

• Project/Area Number: 18KK0255
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Hori Osamu 金沢大学, 医学系, 教授 (60303947)
• Co-Investigator(Kenkyū-buntansha): 宝田 美佳 金沢大学, 医学系, 助教 (40565412) ; 石井 宏史 金沢大学, 医学系, 助教 (90634171)
• Project Period (FY): 2018-10-09 – 2024-03-31
• Keywords: 脳血管障害 / RAGE

Outline of Final Research Achievements

To prevent cerebral vasospasm and symptom exacerbation after subarachnoid hemorrhage (SAH), the researchers, in collaboration with Professor Ann Marie Schmidt of New York University, USA, administered compound 11, a novel RAGE inhibitor, to mice and investigated its effect on the pathological state after SAH. As a result, they confirmed that the compound markedly improved neurological symptoms and cerebral vasospasm. Furthermore, the researchers employed cell-specific RAGE-conditional knockout (cKO) mice and found that neutrophil-derived RAGE plays an important role in the pathogenesis of post-SAH.

Free Research Field

神経解剖学

Academic Significance and Societal Importance of the Research Achievements

今後、RAGE阻害物質によるくも膜下出血後の攣縮予防や神経病態の改善、というこれまでにない視点での臨床研究が期待される。また、本研究を通じて、くも膜下出血の病態形成に重要である早期脳損傷の形成に交感神経系の過活動が重要であることも明らかにすることができた(Demura et al., Stroke. 2022)。今後、くも膜下出血後の病態、特に早期脳損傷と交感神経系の過活動、更にRAGEとの関連が明らかになることが期待される。