Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo, Israel.
Biological Regulation Department, The Weizmann Institute of Science, Rehovot, Israel.
Cereb Cortex. 2021 Jan 1;31(1):248-266. doi: 10.1093/cercor/bhaa223.
Loss of cognitive function with aging is a complex and poorly understood process. Recently, clinical research has linked the occurrence of cortical microinfarcts to cognitive decline. Cortical microinfarcts form following the occlusion of penetrating vessels and are considered to be restricted to the proximity of the occluded vessel. Whether and how such local events propagate and affect remote brain regions remain unknown. To this end, we combined histological analysis and longitudinal diffusion tensor imaging (DTI), following the targeted-photothrombotic occlusion of single cortical penetrating vessels. Occlusions resulted in distant tissue reorganization across the mouse brain. This remodeling co-occurred with the formation of a microglia/macrophage migratory path along subcortical white matter tracts, reaching the contralateral hemisphere through the corpus callosum and leaving a microstructural signature detected by DTI-tractography. CX3CR1-deficient mice exhibited shorter trail lengths, differential remodeling, and only ipsilateral white matter tract changes. We concluded that microinfarcts lead to brain-wide remodeling in a microglial CX3CR1-dependent manner.
随着年龄的增长，认知功能的丧失是一个复杂且尚未被充分理解的过程。最近，临床研究将皮质微梗死的发生与认知能力下降联系起来。皮质微梗死是在穿透性血管闭塞后形成的，被认为仅限于闭塞血管的附近。这种局部事件是否以及如何传播并影响大脑的远程区域尚不清楚。为此，我们结合组织学分析和纵向扩散张量成像（DTI），对单个皮质穿透性血管的靶向光血栓形成闭塞进行了研究。闭塞导致了小鼠大脑中远处组织的重组。这种重塑与小胶质细胞/巨噬细胞迁移途径的形成同时发生，沿着皮质下白质束到达对侧半球，通过胼胝体离开，留下 DTI 轨迹检测到的微观结构特征。CX3CR1 缺陷型小鼠表现出较短的追踪长度、不同的重塑，以及仅同侧白质束的变化。我们得出结论，微梗死以小胶质细胞 CX3CR1 依赖性的方式导致全脑重塑。
