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Ferroptosis in oligodendrocyte progenitor cells mediates white matter injury after hemorrhagic stroke.


ABSTRACT: Oligodendrocyte progenitor cells (OPCs) differentiate to myelin-producing mature oligodendrocytes and enwrap growing or demyelinated axons during development and post central nervous diseases. Failure of remyelination owing to cell death or undifferentiation of OPCs contributes to severe neurologic deficits and motor dysfunction. However, how to prevent the cell death of OPCs is still poorly understood, especially in hemorrhagic diseases. In the current study, we injected autologous blood into the mouse lateral ventricular to study the hemorrhage-induced OPC cell death in vivo. The integrity of the myelin sheath of the corpus callosum was disrupted post intraventricular hemorrhage (IVH) assessed by using magnetic resonance imaging, immunostaining, and transmission electron microscopy. Consistent with the severe demethylation, we observed massive cell death of oligodendrocyte lineages in the periventricular area. In addition, we found that ferroptosis is the major cell death form in Hemin-induced OPC death by using RNA-seq analysis, and the mechanism was glutathione peroxidase 4 activity reduction-resulted lipid peroxide accumulation. Furthermore, inhibition of ferroptosis rescued OPC cell death in vitro, and in vivo attenuated IVH-induced white matter injury and promoted recovery of neurological function. These data demonstrate that ferroptosis is an essential form of OPC cell death in hemorrhagic stroke, and rescuing ferroptotic OPCs could serve as a therapeutic target for stroke and related diseases.

SUBMITTER: Shen D 

PROVIDER: S-EPMC8941078 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Ferroptosis in oligodendrocyte progenitor cells mediates white matter injury after hemorrhagic stroke.

Shen Danmin D   Wu Weihua W   Liu Jing J   Lan Ting T   Xiao Zhongnan Z   Gai Kaiyuan K   Hu Liye L   Luo Zhaoli Z   Wei Chao C   Wang Xiaotong X   Lu Yabin Y   Wang Yamei Y   Zhang Chenguang C   Wang Peipei P   Zuo Zhentao Z   Yang Fei F   Li Qian Q  

Cell death & disease 20220323 3


Oligodendrocyte progenitor cells (OPCs) differentiate to myelin-producing mature oligodendrocytes and enwrap growing or demyelinated axons during development and post central nervous diseases. Failure of remyelination owing to cell death or undifferentiation of OPCs contributes to severe neurologic deficits and motor dysfunction. However, how to prevent the cell death of OPCs is still poorly understood, especially in hemorrhagic diseases. In the current study, we injected autologous blood into t  ...[more]

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