Development of therapeutic methods by controlling migration of glial cells and inflammatory cells in injured spinal cord

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19587
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kyushu University
• Principal Investigator: Kobayakawa Kazu 九州大学, 大学病院, 助教 (40772322)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: アストロサイト / 脊髄損傷 / マクロファージ / 遊走

Outline of Final Research Achievements

It has been shown that ATP secreted by macrophages after spinal cord injury becomes ADP, which reacts with reactive astrocyte P2Y1 receptors and promotes migration through intracellular signaling. On the other hand, when MRS-2179, an inhibitor of the P2Y1 receptor, was injected intrathecally after spinal cord injury, it was found that the migration of astrocytes was inhibited. These results indicate that ATP secreted by macrophages that migrated and aggregated to the injury center became ADP, and that this ADP promoted migration via P2Y1R of reactive astrocytes.

Free Research Field

整形外科学、中枢神経損傷

Academic Significance and Societal Importance of the Research Achievements

脊髄への直接の外力による一次損傷の後、マクロファージ等の炎症細胞による炎症によって起きる続発的な二次損傷が脊髄損傷を重症化させると考えられてきた。しかし今回の結果は、「これまで有害な現象とされてきた炎症細胞の遊走」が、脊髄組織修復に重要なアストロサイトの遊走を促進する事により、組織修復と運動機能回復に貢献している事が示された。今後の更なる研究により、アストロサイトの遊走を実質的に促し、炎症細胞をより狭い範囲へ収束させ、軸索伸展・再生阻害因子であるグリア瘢痕を縮小する事に成功すれば、炎症細胞浸潤抑制主義一辺倒の世界の研究の潮流に変革をもたらす重要な知見を本研究は示している。