2022 Fiscal Year Final Research Report
Role of meningeal lymphatics for traumatic brain injury
Project/Area Number |
19K10695
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 58040:Forensics medicine-related
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Research Institution | Tokyo Women's Medical University |
Principal Investigator |
Shimada Ryo 東京女子医科大学, 医学部, 准教授 (10376725)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | 髄膜リンパ管内皮細胞 / フローサイトメントリ / セルソータ / Microarray / mRNA発現 / ELISA / タンパク発現 |
Outline of Final Research Achievements |
The meningeal lymphatics (ML) transport cerebrospinal fluid and brain tissue fluid to the deep anterior cervical lymph nodes via the shallow and deep cervical lymphatics. To capture ML vessel damage in traumatic brain injury (TBI), we used a mouse model of TBI and analyzed changes in mRNA and protein expression in meningeal lymphatic endothelial cells (MLECs) collected by cell sorter from the meninges after creation of brain injury. The number of MLECs was significantly decreased in the injured group compared to the sham group. The mRNA expression of LYVE1, which is specifically expressed in LECs, in MLECs was significantly decreased in the injured group. On the other hand,mRNA and protein expression of FLT4 and NRP2, which are involved in lymphangiogenesis, in MLECs was significantly increased in the injured group. The results confirmed the impairment and neogenesis of MLECs in traumatic brain injury, suggesting their involvement in the pathogenesis of meningeal lymphangiopathy.
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Free Research Field |
法医学病理、脳神経外傷
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Academic Significance and Societal Importance of the Research Achievements |
晩年のアルツハイマー病や認知症のリスクの増加は、若年時の中等度および重度の脳損傷に関連している。多くのヒトは早期の脳損傷の症状としては完全に回復したが、新たな認知症状は脳損傷後数十年で現れる。脳損傷時と晩年の間に多くの事象および暴露が脳損傷による障害と相互作用する可能性があるか、あるいは認知症のリスクに寄与する可能性がある。これらの要因に関する客観的な情報はほとんどない。本研究は若年外傷性脳損傷での髄膜リンパ管内皮細胞の障害と新生が確認され、髄膜リンパ管障害の病態への関与が示唆された。今後、髄膜リンパ管障害が晩年脳に及ぼす影響の解析を予定している。
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