Ferroptosis of pericyte during brain ischemia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09373
• 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: Kyushu University
• Principal Investigator: Ago Tetsuro 九州大学, 医学研究院, 准教授 (30514202)
• Co-Investigator(Kenkyū-buntansha): 中村 晋之 九州大学, 大学病院, 助教 (80713742)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 脳梗塞 / 虚血再灌流 / ペリサイト / フェロトーシス / 組織修復 / 神経機能回復 / 鉄

Outline of Final Research Achievements

Iron is an essential element requiring various biological responses and causing oxidative stress. Under conditions that oxygen concentrations are rapidly changed, such as ischemia-reperfusion, disturbed intracellular metabolism of iron can cause ferroptosis, an iron-dependent cell death, in some cell types. Reperfusion therapy is established in acute ischemic stroke in human. Nevertheless, no-reflow phenomenon or worsening of damages can occasionally be found even following successful reperfusion. In this study, we have demonstrated that microvascular pericytes, rather than neuronal cells, are more susceptible for ferroptosis in acute ischemic stroke accompanied by reperfusion and that inhibition of pericyte ferroptosis can be a therapeutic target in terms of post-stroke functional recovery.

Free Research Field

脳血管障害

Academic Significance and Societal Importance of the Research Achievements

脳梗塞は日本人の代表的国民病である．超急性期における血栓溶解薬投与やカテーテル治療による再灌流療法が確立したが，その恩恵を受ける患者は10%に満たない．他方，リハビリテーション治療を除き神経機能回復を促進する治療は未だ存在しない．脳梗塞直後の神経保護療法は再灌流療法抜きに無効であることが証明されたが，治療開始に時間的余裕のある機能回復促進療法は，種々の臨床疫学研究，基礎研究の成果からも有望であると考えられる．疾病重症度やその頻度を考えると機能回復促進療法の開発は急務である．脳梗塞後に生じる内因性機能回復機構を明らかにするとともに，その標的細胞を明確にした点で本成果は意義あるものと考えている．