中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (3): 636-641.doi: 10.4103/1673-5374.380903

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

感觉运动皮质缺血后皮质脊髓束Wallerian变性的可视化

  

  • 出版日期:2024-03-15 发布日期:2023-09-02
  • 基金资助:
    国家自然科学基金项目(31730030,81941011,31771053,82271403,82272171,31971279和82201542);北京市自然科学基金项目(7222004);北京市科技计划项目(Z181100001818007)

Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

Jiao Mu1, Liufang Hao2, Zijue Wang2, Xuyang Fu2, Yusen Li2, Fei Hao1, Hongmei Duan2, Zhaoyang Yang2, *, Xiaoguang Li1, 2, *   

  1. 1Beijing Key Laboratory for Biomaterials and Neural Regeneration, School of Biological Science and Medical Engineering, Beihang University, Beijing, China; 2Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
  • Online:2024-03-15 Published:2023-09-02
  • Contact: Xiaoguang Li, PhD, lxgchina@sina.com or zzgc811@163.com; Zhaoyang Yang, PhD, wack_lily@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 31730030 (to XL), 81941011 (to XL), 31771053 (to HD), 82271403 (to XL), 82272171 (to ZY), 31971279 (to ZY), and 82201542 (to FH); the Natural Science Foundation of Beijing, No. 7222004 (to HD); the Science and Technology Program of Beijing, No. Z181100001818007 (to ZY).

摘要:

脑卒中可导致脑外远端区域的Wallerian变性,尤其是对于皮质脊髓束。为研究脑卒中后受影响的皮质脊髓束内神经胶质细胞和轴突的命运,实验以光化学诱导小鼠感觉运动皮质梗死,以在全部皮质脊髓束范围内诱导Wallerian变性。首先使用轴突损伤常规敏感标志物淀粉样β前体蛋白来检测皮质脊髓束的Wallerian变性。结果显示,Wallerian变性仅能定位于缺血皮质内的近端轴突,不能到达皮质脊髓束远端。为提高Wallerian变性的可视化,利用表达绿色荧光蛋白的顺行示踪病毒来标记皮质脊髓束,通过定量评估表达绿色荧光蛋白的轴突可准确地显示,轴突变性开始于脑卒中后第3天,并在脑卒中后7d内完成。此外,小胶质细胞从脑卒中后第7天起就开始动员并激活,但随着时间的推移其无法维持吞噬状态。同时,星形胶质细胞表现出相对延迟的动员,并对Wallerian变性表现出适度反应。皮质脊髓束的Wallerian变性没能诱导脊髓前角细胞的顺行性变性。这一结果为皮质脊髓束内Wallerian变性期间主要细胞成分提供了动态变化的时空证据。

https://orcid.org/0000-0001-8313-6998 (Zhaoyang Yang); https://orcid.org/0000-0003-4480-3676 (Xiaoguang Li)

关键词: Wallerian变性, 皮质脊髓束, 脑卒中, 轴突变性, 绿色荧光蛋白, 小胶质细胞, 星形胶质细胞, 病毒示踪

Abstract: Stroke can cause Wallerian degeneration in regions outside of the brain, particularly in the corticospinal tract. To investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke, we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal tract. We first used a routine, sensitive marker of axonal injury, amyloid precursor protein, to examine Wallerian degeneration of the corticospinal tract. An antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex, with no positive signal in distal parts of the corticospinal tract, at all time points. To improve visualization of Wallerian degeneration, we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing axons. Using this approach, we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after stroke. In addition, microglia mobilized and activated early, from day 7 after stroke, but did not maintain a phagocytic state over time. Meanwhile, astrocytes showed relatively delayed mobilization and a moderate response to Wallerian degeneration. Moreover, no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal tract. In conclusion, our data provide evidence for dynamic, pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

Key words: corticospinal tract, green fluorescent protein, microglia, spinal anterior horn cells, stroke, virus trace, Wallerian degeneration