Single Cortical Microinfarcts Lead to Widespread Microglia/Macrophage Migration along the White Matter

Alisa Lubart, Amit Benbenishty, Hagai Har-Gil, Hadas Laufer, Amos Gdalyahu, Yaniv Assaf, Pablo Blinder*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)248-266
Number of pages19
JournalCerebral Cortex
Volume31
Issue number1
DOIs
StatePublished - 1 Jan 2021

Keywords

  • cortical microinfarct
  • diffusion tensor imaging
  • microglia/macrophages
  • myelin
  • targeted photothrombotic occlusion

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