Strategy for reconstruction of the injured white matter in spinal cord injuries

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09459
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kyoto University
• Principal Investigator: Nishio Takeshi 京都大学, 医学研究科, 客員研究員 (70303790)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 脊髄損傷 / 軸索グリア複合体 / 再生的パイオニア軸索 / 白質再建

Outline of Final Research Achievements

After transection of the spinal cord in adult rats, some of severed axons start regeneration within 2 hours of section and can reach the lesion site within 3 hours, which we named as "regenerative pioneering axons; RPA". We also found at the lesion site an abnormal structure that consisted of axon fragments and glial processes, which we named as "axonoglial complex, AGC". The spatiotemporal relationship between the RPA and AGC suggested the AGC would be an obstacle against the RPA.
The present study tried to remove the AGC through a surgical technique or a chemical digestion with some proteases, and found that the RPA could penetrate the lesion site within several hours of section growing along the original white matter.
Thus, the present study has revealed an effectiveness of a new strategy to modify the injured white matter in acute phase removing the"AGC" at the lesion site.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

脊髄損傷患者では、しばしば損傷後の麻痺は永続する。その主因として「損傷部を越える中枢神経軸索の再生は制限されている事」が挙げられる。即ち、神経軸索が損傷部を越えて再生できれば、損傷された神経ネットワークを再構築することができ、脊髄機能も回復できる。
本研究では、成熟ラットの脊髄切断モデルを用いて、切断後数時間という早期の変化に着目し、旺盛な再生能力を持つパイオニア軸索に対して、切断部に生じる早期の障害物を除去すれば、パイオニア軸索は切断部を超えて本来の白質経路を伸長できることを示した。この結果は脊髄損傷の新たな治療戦略を示した。