Abstract

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.

中文翻译：

---

单个皮质微梗死导致沿白质广泛的小胶质细胞/巨噬细胞迁移。

摘要

随着年龄的增长，认知功能的丧失是一个复杂且知之甚少的过程。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。皮层微梗死在穿透血管闭塞后形成，被认为仅限于闭塞血管的附近。这些局部事件是否以及如何传播和影响远程大脑区域仍然未知。为此，我们结合组织学分析和纵向扩散张量成像 (DTI)，在单个皮质穿透血管的靶向光血栓形成闭塞之后。闭塞导致整个小鼠大脑的远处组织重组。这种重塑与沿着皮层下白质束形成小胶质细胞/巨噬细胞迁移路径共同发生，通过胼胝体到达对侧半球，并留下 DTI 纤维束成像检测到的微观结构特征。CX3CR1 缺陷小鼠表现出较短的路径长度、差异重塑和仅同侧白质束变化。我们得出结论，微梗死以小胶质细胞 CX3CR1 依赖性方式导致全脑重塑。