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Single Cortical Microinfarcts Lead to Widespread Microglia/Macrophage Migration Along the White Matter
Alisa Lubart1, Amit Benbenishty1,2, Hagai Har-Gil1
1Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo, Israel.
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.
Insights
Cortical microinfarcts trigger widespread brain remodeling. This process involves microglia migration along white matter tracts and is dependent on the CX3CR1 receptor, impacting cognitive function during aging.
Area of Science:
- Neuroscience
- Neuropathology
- Aging Research
Background:
- Cognitive decline with aging is a significant challenge.
- Cortical microinfarcts, resulting from vessel occlusion, are linked to cognitive impairment.
- The propagation of microinfarcts to remote brain regions is not well understood.
Purpose of the Study:
- To investigate how localized cortical microinfarcts affect remote brain regions.
- To elucidate the mechanisms underlying microinfarct-induced brain-wide remodeling.
- To determine the role of microglial CX3CR1 in this process.
Main Methods:
- Targeted photothrombotic occlusion of single cortical penetrating vessels in mice.
- Longitudinal diffusion tensor imaging (DTI) for microstructural analysis.
- Histological examination to track cellular changes and tissue reorganization.
Main Results:
- Occlusion induced distant tissue reorganization across the brain.
- A microglia/macrophage migratory path formed along white matter tracts, extending to the contralateral hemisphere.
- CX3CR1-deficient mice showed limited remodeling and only ipsilateral white matter changes.
- DTI-tractography detected microstructural signatures of this remodeling.
Conclusions:
- Microinfarcts initiate brain-wide remodeling.
- This remodeling is dependent on microglial CX3CR1 signaling.
- Microglial migration along white matter tracts is a key component of the brain's response to microinfarcts.
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