2022 Fiscal Year Final Research Report
Pathophysiological analysis and development of therapy in partial reperfusion in ischemic stroke
| Project/Area Number |
20K09388
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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 | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中神 啓徳 大阪大学, 大学院医学系研究科, 寄附講座教授 (20325369)
林 宏樹 大阪大学, 大学院医学系研究科, 寄附講座講師 (20813364)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 脳梗塞 / 炎症 / 神経細胞死 / 血液脳関門 / LGR4 |
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| Outline of Final Research Achievements |
In the present study, a novel model of partial recanalization in mice was developed. Partial recanalization was shown to induce more apoptosis at 3 hours, with delayed degeneration of injured neurons occurring between 3 and 24 hours although the final infarct size was the same as that of permanent occlusion. FITC-labeled dextran could reach the infarction site, suggesting that drug delivery to the infarction site is possible with partial recanalization. In partial realization, expression of LGR4 was downregulated in the infarct region but maintained at the infarction site on days 1 and 3 compared to the normal site. It was expressed on neurons at the normal region and on injured neurons and microglia/macrophages at the infarct region. Unfortunately, no therapeutic effect was observed with MHP1, which is a partial peptide of RANKL.
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| Free Research Field |
虚血性脳血管障害
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| Academic Significance and Societal Importance of the Research Achievements |
脳梗塞において、血栓回収療法が不完全な状態（部分再開通）では予後が改善せず、新たな治療法の開発が必要とされているが、その病態は明らかではなかった。新たに作成した部分再開通モデルマウスを用いた検討では、永久閉塞と比較すると部分再開通では神経細胞死が遅延し、アポトーシス細胞が増加すること、また、血液脳関門の破綻が軽度であり、静脈内に投与された薬剤の梗塞部位への到達が可能であることが示唆された。これらの結果から、部分再開通が脳梗塞において治療対象となること、また、薬剤開発のために必要な基礎的な病態が明らかとなった。
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