Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China.
Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
J Cereb Blood Flow Metab. 2022 May;42(5):757-770. doi: 10.1177/0271678X211065391. Epub 2021 Dec 8.
White matter injury is a critical pathological characteristic during ischemic stroke. Oligodendrocyte precursor cells participate in white matter repairing and remodeling during ischemic brain injury. Since oligodendrocyte precursor cells could promote Wnt-dependent angiogenesis and migrate along vasculature for the myelination during the development in the central nervous system, we explore whether exogenous oligodendrocyte precursor cell transplantation promotes angiogenesis and remyelination after middle cerebral artery occlusion in mice. Here, oligodendrocyte precursor cell transplantation improved motor and cognitive function, and alleviated brain atrophy. Furthermore, oligodendrocyte precursor cell transplantation promoted functional angiogenesis, and increased myelin basic protein expression after ischemic stroke. The further study suggested that white matter repairing after oligodendrocyte precursor cell transplantation depended on angiogenesis induced by Wnt/β-catenin signal pathway. Our results demonstrated a novel pathway that Wnt7a from oligodendrocyte precursor cells acting on endothelial β-catenin promoted angiogenesis and improved neurobehavioral outcomes, which facilitated white matter repair and remodeling during ischemic stroke.
脑白质损伤是缺血性脑卒中的一个关键病理特征。少突胶质前体细胞在缺血性脑损伤中参与白质的修复和重塑。由于少突胶质前体细胞在中枢神经系统发育过程中能够促进 Wnt 依赖性血管生成，并沿着血管迁移进行髓鞘形成，因此我们探讨了外源性少突胶质前体细胞移植是否能促进大脑中动脉闭塞后小鼠的血管生成和髓鞘再生。结果显示，少突胶质前体细胞移植改善了运动和认知功能，并减轻了脑萎缩。此外，少突胶质前体细胞移植促进了缺血性脑卒中后的功能性血管生成，并增加了髓鞘碱性蛋白的表达。进一步的研究表明，少突胶质前体细胞移植后的白质修复依赖于 Wnt/β-catenin 信号通路诱导的血管生成。我们的研究结果表明，少突胶质前体细胞中的 Wnt7a 通过作用于内皮细胞中的 β-catenin 来促进血管生成，并改善神经行为学结局，从而有利于缺血性脑卒中期间的白质修复和重塑。
