2022 Fiscal Year Final Research Report
Investigation for therapeutic effects of exosomes on post-stroke glial scar formation and axonal regeneration
| Project/Area Number |
20K07909
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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 52020:Neurology-related
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| Research Institution | University of Yamanashi (2022)
Juntendo University (2020-2021) |
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Principal Investigator |
Ueno Yuji 山梨大学, 大学院総合研究部, 教授 (00349002)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 脳梗塞 / エクソソーム / 細胞外膜小胞 / マイクログリア / アストロサイト / 機能回復 |
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| Outline of Final Research Achievements |
The purpose of the present study is to elucidate the molecular mechanisms that regulate the glial scar formation by exosomes in the chronic phase of cerebral infarction, for facilitating axonal regeneration and functional recovery. Administration of microglia-conditioned media (MCM) and P2Y1 receptor antagonist reduced the expression of inflammatory genes, and downregulated MAPK/NF-κB/TNF-α/IL-1β signals in cultured astrocytes after ischemia. Furthermore, treatment with exosomes derived from the anti-inflammatory cultured astrocytes, enriched miR-146a-5p, to the peri-infarct area, decreased the expression of NF-κB and TNF-α in reactive astrocytes, increased pNFH+ axonal regeneration, and thereby improved motor function after stroke.
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| Free Research Field |
神経内科学
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| Academic Significance and Societal Importance of the Research Achievements |
炎症が脳梗塞慢性期においても依然存在し、グリア瘢痕の形成に重要であることを確認した。マイクログリアがアストロサイトの炎症制御に関与し、炎症が抑制されたグリア瘢痕は軸索再生や機能回復を促進させる環境となりうることがわかった。アストロサイト由来エクソソーム中のmiR-146a-5pが抗炎症作用を有し、グリア瘢痕制御により、脳梗塞後遺症改善を目的とした新規治療薬となる可能性が示された。
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