Mu Jiao, Hao Liufang, Wang Zijue, Fu Xuyang, Li Yusen, Hao Fei, Duan Hongmei, Yang Zhaoyang, Li Xiaoguang
Beijing Key Laboratory for Biomaterials and Neural Regeneration, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Neural Regen Res. 2024 Mar;19(3):636-641. doi: 10.4103/1673-5374.380903.
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.
中风可导致大脑以外区域的华勒氏变性，尤其是在皮质脊髓束。为了研究中风后皮质脊髓束受累区域内主要神经胶质细胞和轴突的命运，我们诱导了感觉运动皮层的光化学梗死，导致皮质脊髓束全长出现华勒氏变性。我们首先使用一种常规的、敏感的轴突损伤标志物——淀粉样前体蛋白，来检测皮质脊髓束的华勒氏变性。在所有时间点，针对淀粉样前体蛋白的抗体仅定位在缺血皮层内的近端轴突段，在皮质脊髓束的远端没有阳性信号。为了更好地观察华勒氏变性，我们接下来利用一种表达绿色荧光蛋白的顺行病毒标记皮质脊髓束，然后对表达绿色荧光蛋白的轴突进行定量评估。使用这种方法，我们发现轴突变性在中风后第3天开始，在中风后7天几乎完全完成。此外，小胶质细胞在中风后第7天开始早期动员和激活，但随着时间的推移并没有维持吞噬状态。与此同时，星形胶质细胞的动员相对延迟，对华勒氏变性的反应适中。此外，未观察到脊髓前角细胞因皮质脊髓束的华勒氏变性而发生顺行性变性。总之，我们的数据为华勒氏变性过程中皮质脊髓束主要细胞成分的动态、致病性时空变化提供了证据。
