| Project/Area Number |
22K09274
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
Hokari Masaaki 北海道大学, 医学研究院, 客員研究員 (30622807)
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| Co-Investigator(Kenkyū-buntansha) |
藤村 幹 北海道大学, 医学研究院, 教授 (00361098)
川堀 真人 北海道大学, 医学研究院, 講師 (50399870)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Completed (Fiscal Year 2024)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2024: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 脳虚血 / 間葉系幹細胞 / エクソソーム |
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| Outline of Research at the Start |
「心停止・重症SAH・低酸素・外傷性脳圧亢進」等によってもたらされる「広範性脳損傷」は「難治性の意識障害（遷延性意識障害）」をもたらし、その治療法の開発は急務である。本研究は「間葉系幹細胞」から分泌され神経保護作用を有する「エクソソーム」を「高濃度で脳内に到達させる」ため「経鼻的投与法」を採用し、その治療効果を検討する。①異なる時間軸での効果検証（「急性期」および「慢性期」投与に対するエクソソームの脳内分布と治療効果）、そしてその新規的作用機序である②「脳-腸」相関機構の解明を目指す。
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| Outline of Final Research Achievements |
Hypoxic-ischemic brain injury (HIBI) lacks effective treatments. Recent studies have suggested that exosomes derived from mesenchymal stem cells may have therapeutic potential. This study investigates the effects of intranasally administered exosomes in an animal model. Exosomes were isolated via ultracentrifugation, and HIBI was induced in Sprague-Dawley rats using a transient four-vessel occlusion model. Rats were treated with 3 × 10e8 exosome particles in 20 uL of PBS for 7 days post-injury. Cognitive assessments, exosome biodistribution, and histological analysis were performed. Exosomes were initially detected in the olfactory bulb, then distributed to the striatum and midbrain. Rats treated with exosomes showed significant cognitive improvements, fewer apoptotic cells, and higher neuronal survival in the hippocampus. Exosomes also reduced inflammatory markers in microglia. These results indicate exosome-based therapy could offer a novel treatment for HIBI.
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| Academic Significance and Societal Importance of the Research Achievements |
低酸素脳症という治療法が全く存在しない疾病に対して経鼻的なエクソソーム投与が死亡率抑制、高次脳機能改善をもたらすこと、その作用機序や脳内の分布なども確認することが出来た。今後臨床応用によって多くの患者が救われる可能性があると考える。
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