Analysis of cerebral ischemic neural cell death and ferroptosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07814
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Takasaki University of Health and Welfare (2021-2022); Gunma University (2019-2020)
• Principal Investigator: Kubota Chisato 高崎健康福祉大学, 健康福祉学部, 助教 (90750638)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 脳虚血 / フェロトーシス / 脂質過酸化

Outline of Final Research Achievements

Oxidative stress-associated cell death is implicated in cerebral ischemia-associated neural damage. Recently, a cell death pathway that involved reactive oxygen species production has been shown in tumor cells and named ferroptosis due to an iron-dependence. We revealed that lipoxygenase, intracellular free iron, and the accumulation of lipid reactive oxygen species are involved in glutamate induced cell death.
We found that volatilized 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) effectively prevented both ferroptosis and glutamate-induced oxidative toxicity in mouse neuronal cell line. Furthermore, TEMPO clearly reduced neural cell death in a middle cerebral artery occlusion (MCAO) model in mouse. We suggest potential physiological relevance of ferroptosis and neural cell injury during periods of ischemia.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

脳梗塞は時に致命的となる疾患で、脳組織障害の機序を明らかにし脳保護を果たす方法を示すことは社会的に重要である。本研究から、虚血による神経細胞死の機構の一端が明らかとなり、また神経保護剤として応用されうる化合物を示した。