Development of novel therapeutic approach for subarachnoid hemorrhage: inhibition mTOR pathway by rapamycin

Research Project

Project/Area Number	17K11563
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Emergency medicine
Research Institution	Akita Cerebrospinal and Cardiovascular Center (2021) Tohoku University (2017-2020)
Principal Investigator	Sasaki Kazumasu 秋田県立循環器・脳脊髄センター(研究所), その他部局等, 主任研究員 (80738948)
Co-Investigator(Kenkyū-buntansha)	武藤達士東北大学, 加齢医学研究所, 准教授 (80462472)
Project Period (FY)	2017-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords	mTOR / くも膜下出血 / 早期脳損傷 / 脳保護 / 神経炎症 / 加齢 / マウスくも膜下出血モデル / 蘇生 / 加齢医学 / 加齢促進モデルマウス
Outline of Final Research Achievements	This study investigated the neuroprotective effects of the mammalian target of rapamycin (mTOR) on the early brain injury in the murine model of subarachnoid hemorrhage. We studied aged mice (80-90 weeks) as a model of the pathology of the elderly. Briefly, we confirmed that the mTOR has a therapeutic effect on enhanced recovery from decreased cerebral blood flow and locomotor activity after the induction of SAH. Further, our results showed that the mTOR inhibits the increased number of glial cells after the ischemic injury. These findings provide basic information regarding the neuroprotective role of mTOR against microvascular ischemic injury after SAH in the aged brain.
Academic Significance and Societal Importance of the Research Achievements	本研究では、加齢性変化を考慮したSAH後の早期脳損傷に対するmTOR活性阻害剤の脳保護効果を明らかにした。本研究のみでその全容を明らかにする事は困難であるが、高齢者のSAHの予後改善に寄与するmTOR経路を介した新たな薬物療法開発への可能性を提示した。