2. Academic Validation
  3. Ferroptosis in oligodendrocyte progenitor cells mediates white matter injury after hemorrhagic stroke

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

  • Cell Death Dis. 2022 Mar 23;13(3):259. doi: 10.1038/s41419-022-04712-0.
Danmin Shen 1,  Weihua Wu 1,  Jing Liu 2,  Ting Lan 1,  Zhongnan Xiao 1,  Kaiyuan Gai 3,  Liye Hu 1,  Zhaoli Luo 1,  Chao Wei 2,  Xiaotong Wang 2,  Yabin Lu 1,  Yamei Wang 1,  Chenguang Zhang 1,  Peipei Wang 2,  Zhentao Zuo 4 5 6,  Fei Yang 2 7,  Qian Li 8 9
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
  • 2 Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
  • 3 School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
  • 4 State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • 5 Hefei Comprehensive National Science Center, Institute of Artificial Intelligence, Hefei, China.
  • 6 Sino-Danish College, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 7 Advanced Innovation Center for Human Brain Protection, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, 100069, China.
  • 8 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China. qianli@ccmu.edu.cn.
  • 9 Advanced Innovation Center for Human Brain Protection, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, 100069, China. qianli@ccmu.edu.cn.
PMID: 35318305 DOI: 10.1038/s41419-022-04712-0
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.

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