Distribution of CCL21 and activated microglia in spinal cord-related pain

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09059
• 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: University of Fukui
• Principal Investigator: Hirai Takayuki 福井大学, 学術研究院医学系部門, 特別研究員 (30569132)
• Co-Investigator(Kenkyū-buntansha): 中嶋 秀明 福井大学, 学術研究院医学系部門, 講師 (10397276)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 脊髄損傷 / 神経障害性疼痛 / ミクログリア / マクロファージ / CCL21 / pltマウス

Outline of Final Research Achievements

CCL21 is a chemokine that activates microglia in the central nervous system. In this study we used an SCI model in mutant (plt) mice with deficient CCL21 expression. SCI-induced hypersensitivities to mechanical and thermal stimulation were relieved in plt mice. In immunohistochemical analysis, the phenotype of microglia/macrophages was M1 type-dominant in both types of mice at the lesion site and lumbar enlargement. A decrease of M1-type microglia/macrophages was seen in plt mice, while the number of M2-type microglia/macrophages did not differ between these mice. In immunoblot analysis, expression of M1-induced cytokines was decreased in plt mice, while that of M2-induced cytokines did not differ in the two types of mice. The results indicate that suppression of expression of inflammatory cytokines by decreasing the number of M1-type microglia/macrophages at the injured site and lumbar enlargement is associated with provision of an environment for reduction of neuropathic pain.

Free Research Field

脊椎脊髄病学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、CCL21が血行M1 type の遊走を惹起し、ならびに損傷部の炎症反応の増加に重要な役割を果たしていることを示唆している。 CCL21のこれらの効果は、負傷部位だけでなく、SCI高位以遠である腰膨大部に波及し、NePを誘発した可能性を示した。 これらの結果は、CCL21がSCI後のNePに重要なサイトカインでありSCI後のNePを緩和するための新しい治療法となる可能性がある。