Investigation into the human-specific mechanism of tissue repair and inflammation control at the glial scar of brain infarcts.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17011
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Fukuoka Dental College (2021); Kyushu University (2019-2020)
• Principal Investigator: Shijo Masahiro 福岡歯科大学, 口腔歯学部, 助教 (80822155)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脳梗塞 / グリア瘢痕 / アストロサイト / ミクログリア / ANXA1 / 制御性T細胞 / CCL20

Outline of Final Research Achievements

Using immunohistochemistry, we assessed the altered distribution of ANXA1, one of the anti-inflammatory proteins, and expression pattern of T cell-chemokines and their receptors in the peri-infarct glial scar of human brain infarcts using 14 autopsied samples and 18 surgical samples. Elevated expression of ANXA1 was observed in reactive astrocytes in peri-infarct regions. ANXA1 accumulated at the cell periphery and in swollen cytoplasmic processes of reactive astrocytes, as well as at the rim of vacuoles at the boundary of necrosis, and co-localized with aberrantly distributed AQP4 and EAAT1. Foamy macrophages in the necrotic core also expressed abundant ANXA1, whereas resident microglia at the boundary of necrosis rarely showed intrinsic expression. CCR6-positive regulatory T cells tended to locate near the boundary of necrosis, and CCL20 in astrocytes also accumulate in swollen cytoplasmic processes showing partial co-localization with ANXA1 and several astrocytic markers.

Free Research Field

神経病理学

Academic Significance and Societal Importance of the Research Achievements

脳梗塞辺縁のアストロサイト・ミクログリアや梗塞内部マクロファージとの間のANXA1やT細胞遊走ケモカインの発現差異が明らかとなり、特に梗塞周囲グリア瘢痕のアストロサイトにおける虚血時の浮腫・グルタミン酸負荷応答としてのANXA1発現・細胞内局在変化やCCL20による梗塞辺縁へのTreg誘導を通した、脳梗塞辺縁の炎症制御の可能性を示した。
これらの結果は既報の動物実験結果とは異なるヒト特有の挙動の可能性があり、脳梗塞におけるヒト特有の修復・炎症制御機構の究明に寄与し、ひいては今後の脳梗塞治療法開発の基盤となる事が期待される。