2024 Fiscal Year Final Research Report

Fine structure and MRI image of the neurofluid drainage system in the human cerebral meninges, spinal nerve sheath

Research Project

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Project/Area Number	22K09289
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56010:Neurosurgery-related
Research Institution	Oita University
Principal Investigator	Miura Masahiro 大分大学, 医学部, 講師 (50199957)
Co-Investigator(Kenkyū-buntansha)	山田茂樹名古屋市立大学, 医薬学総合研究院(医学), 講師 (40422969) 間瀬光人名古屋市立大学, 医薬学総合研究院(医学), 教授 (60238920) 内野哲哉大分大学, 医学部, 講師 (70423697) 高橋浩一国際医療福祉大学, 臨床医学研究センター, 非常勤講師 (90246413)
Project Period (FY)	2022-04-01 – 2025-03-31
Keywords	Neurofluid / 髄液動態 / 脊髄神経根鞘 / MRI / 走査型電子顕微鏡 / 硬膜外リンパ系 / カニクイザル / 脈管外通液路
Outline of Final Research Achievements	Although the central nervous system (CNS) is an organ system with active neuronal metabolism and cerebrospinal fluid dynamics, the detailed site of extra-menigeal clearance in the CNS remains unclear. In this study, we re-examined the importance of a mechanism by which neurofluid is cleared from spinal nerve roots (lower CNS) via the meningeal lymphatic system, rather than the conventionally proposed pathway from the brain level to the main site of absorption. This was demonstrated by monitoring intrathecal gadolinium (Gd) dynamics using MRI in a monkey model. In addition, the dynamics of CH40 carbon particles throughout the central nervous system and laser Gd distribution analysis showed consistency with the MRI results, MRI results, suggesting that the neurofluid outflow pathway through each spinal nerve root is more important than the upper CNS. However, individual differences in CSF dynamics were also observed.
Free Research Field	脳神経外科
Academic Significance and Societal Importance of the Research Achievements	最近、産生機序が混在する脳脊髄液と脳間質液は同質の液体としてNeurofluidと呼ばれている。脳内では活発な神経代謝に伴う代謝産物と大量の間質液排出を担う非リンパ系排出機序、さらに脳室や髄腔におけるNeurofluid排液路はともに詳細は未だ明らかにされていない。本研究において、髄液循環異常に伴う正常圧水頭症、髄液漏出症、さらにアルツハイマー型痴呆症等の病態解明とそれらの治療戦略において、Neurofluidの脳レベルに潜在する排出機序の他に、髄液圧調節に関わる脊髄レベルに稼働する排出路の微細構造と生理的機能を明らかにしたことの学術的意義また社会学的意義は極めて大きいと考えられる。