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创伤性脑损伤后 Wnt/β-catenin 表达上调伴随着血管修复。

Up-regulation of Wnt/β-catenin expression is accompanied with vascular repair after traumatic brain injury.

机构信息

1 Cell, Molecular and Developmental Biology Program, 8790 University of California, Riverside , CA, USA.

2 Department of Pediatrics, 4608 Loma Linda University , Loma Linda, CA, USA.

出版信息

J Cereb Blood Flow Metab. 2018 Feb;38(2):274-289. doi: 10.1177/0271678X17744124. Epub 2017 Nov 21.

Abstract

Recent data suggest that repairing the cerebral vasculature after traumatic brain injury (TBI) may help to improve functional recovery. The Wnt/β-catenin signaling pathway promotes blood vessel formation during vascular development, but its role in vascular repair after TBI remains elusive. In this study, we examined how the cerebral vasculature responds to TBI and the role of Wnt/β-catenin signaling in vascular repair. We induced a moderate controlled cortical impact in adult mice and performed vessel painting to visualize the vascular alterations in the brain. Brain tissue around the injury site was assessed for β-catenin and vascular markers. A Wnt transgenic mouse line was utilized to evaluate Wnt gene expression. We report that TBI results in vascular loss followed by increases in vascular structure at seven days post injury (dpi). Immature, non-perfusing vessels were evident in the tissue around the injury site. β-catenin protein expression was significantly reduced in the injury site at 7 dpi. However, there was an increase in β-catenin expression in perilesional vessels at 1 and 7 dpi. Similarly, we found increased number of Wnt-GFP-positive vessels after TBI. Our findings suggest that Wnt/β-catenin expression contributes to the vascular repair process after TBI.

摘要

最近的数据表明,修复创伤性脑损伤(TBI)后的脑血管可能有助于改善功能恢复。Wnt/β-catenin 信号通路在血管发育过程中促进血管形成,但它在 TBI 后血管修复中的作用仍不清楚。在这项研究中,我们研究了脑血管对 TBI 的反应以及 Wnt/β-catenin 信号在血管修复中的作用。我们在成年小鼠中诱导中度控制性皮质撞击,并进行血管染色以可视化大脑中的血管变化。评估损伤部位周围的脑组织中β-catenin 和血管标志物的表达。利用 Wnt 转基因小鼠系评估 Wnt 基因表达。我们报告 TBI 导致血管丢失,随后在损伤后 7 天(dpi)血管结构增加。在损伤部位周围的组织中可见不成熟、非灌注的血管。β-catenin 蛋白表达在 7 dpi 时在损伤部位显著降低。然而,在 1 和 7 dpi 时,损伤周围血管中的β-catenin 表达增加。同样,我们发现 TBI 后 Wnt-GFP 阳性血管的数量增加。我们的研究结果表明,Wnt/β-catenin 表达有助于 TBI 后的血管修复过程。

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