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

少突胶质细胞前体细胞移植通过 Wnt/β-catenin 信号传导保护小鼠脑缺血模型中的血脑屏障

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作者:Liping Wang, Jieli Geng, Meijie Qu, Fang Yuan, Yuyang Wang, Jiaji Pan, Yongfang Li, Yuanyuan Ma, Panting Zhou, Zhijun Zhang, Guo-Yuan Yang

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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