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  3. Oligodendrocyte precursor cells transplantation protects blood-brain barrier in a mouse model of brain ischemia via Wnt/β-catenin signaling

Oligodendrocyte precursor cells transplantation protects blood-brain barrier in a mouse model of brain ischemia via Wnt/β-catenin signaling

  • Cell Death Dis. 2020 Jan 6;11(1):9. doi: 10.1038/s41419-019-2206-9.
Liping Wang 1 2 3,  Jieli Geng 4,  Meijie Qu 1,  Fang Yuan 2,  Yuyang Wang 1,  Jiaji Pan 2,  Yongfang Li 1,  Yuanyuan Ma 1,  Panting Zhou 2,  Zhijun Zhang 5,  Guo-Yuan Yang 6 7
Affiliations

Affiliations

  • 1 Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
  • 2 Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
  • 3 Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
  • 4 Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China. gengjieli@renji.com.
  • 5 Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China. zhangzj@sjtu.edu.cn.
  • 6 Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China. gyyang@sjtu.edu.cn.
  • 7 Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China. gyyang@sjtu.edu.cn.
PMID: 31907363 DOI: 10.1038/s41419-019-2206-9
Abstract

Blood-brain barrier damage is a critical pathological feature of ischemic stroke. Oligodendrocyte precursor cells are involved in maintaining blood-brain barrier integrity during the development. However, whether oligodendrocyte precursor cell could sustain blood-brain barrier permeability during ischemic brain injury is unknown. Here, we investigate whether oligodendrocyte precursor cell transplantation protects blood-brain barrier integrity and promotes ischemic stroke recovery. Adult male ICR mice (n = 68) underwent 90 min transient middle cerebral artery occlusion. After ischemic assault, these mice received stereotactic injection of oligodendrocyte precursor cells (6 × 105). Oligodendrocyte precursor cells transplantation alleviated edema and infarct volume, and promoted neurological recovery after ischemic stroke. Oligodendrocyte precursor cells reduced blood-brain barrier leakage via increasing claudin-5, occludin and β-catenin expression. Administration of β-catenin Inhibitor blocked the beneficial effects of oligodendrocyte precursor cells. Wnt7a protein treatment increased β-catenin and claudin-5 expression in endothelial cells after oxygen-glucose deprivation, which was similar to the results of the conditioned medium treatment of oligodendrocyte precursor cells on endothelial cells. We demonstrated that oligodendrocyte precursor cells transplantation protected blood-brain barrier in the acute phase of ischemic stroke via activating Wnt/β-catenin pathway. Our results indicated that oligodendrocyte precursor cells transplantation was a novel approach to the ischemic stroke therapy.

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