4.7 Article

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

Journal

CELL DEATH & DISEASE
Volume 11, Issue 1, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41419-019-2206-9

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Funding

  1. Scientific Research and Innovation Program of Shanghai Education Commission [2019-01-07-00-02-E00064]
  2. National Natural Science Foundation of China [81771251, 81771244, 81471178]
  3. National Key Research and Development Program of China [2016YFC1300600]
  4. K. C. Wong Education Foundation
  5. Science and Technology Commission of Shanghai Municipality [17ZR1413600]

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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 90min transient middle cerebral artery occlusion. After ischemic assault, these mice received stereotactic injection of oligodendrocyte precursor cells (6x10(5)). 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 beta -catenin expression. Administration of beta -catenin inhibitor blocked the beneficial effects of oligodendrocyte precursor cells. Wnt7a protein treatment increased beta -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/beta -catenin pathway. Our results indicated that oligodendrocyte precursor cells transplantation was a novel approach to the ischemic stroke therapy.

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