CCR2+ Monocytes Promote White Matter Injury and Cognitive Dysfunction After Myocardial Infarction

Authors

Edward B Thorp
Mallory Filipp
Maria Dima
Chunfeng Tan
Matthew Feinstein
Brian Popko
Matthew DeBerge

Language

English

Publication Date

7-1-2024

Journal

Brain, Behavior, and Immunity

PMID

38735403

PMCID

PMC11574971

PubMedCentral® Posted Date

7-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Survivors of myocardial infarction are at increased risk for vascular dementia. Neuroinflammation has been implicated in the pathogenesis of vascular dementia, yet little is known about the cellular and molecular mediators of neuroinflammation after myocardial infarction. Using a mouse model of myocardial infarction coupled with flow cytometric analyses and immunohistochemistry, we discovered increased monocyte abundance in the brain after myocardial infarction, which was associated with increases in brain-resident perivascular macrophages and microglia. Myeloid cell recruitment and activation was also observed in post-mortem brains of humans that died after myocardial infarction. Spatial and single cell transcriptomic profiling of brain-resident myeloid cells after experimental myocardial infarction revealed increased expression of monocyte chemoattractant proteins. In parallel, myocardial infarction increased crosstalk between brain-resident myeloid cells and oligodendrocytes, leading to neuroinflammation, white matter injury, and cognitive dysfunction. Inhibition of monocyte recruitment preserved white matter integrity and cognitive function, linking monocytes to neurodegeneration after myocardial infarction. Together, these preclinical and clinical results demonstrate that monocyte infiltration into the brain after myocardial infarction initiate neuropathological events that lead to vascular dementia.

Keywords

Animals, Myocardial Infarction, White Matter, Cognitive Dysfunction, Monocytes, Mice, Male, Humans, Brain, Receptors, CCR2, Mice, Inbred C57BL, Disease Models, Animal, Macrophages, Microglia, Neuroinflammatory Diseases, Dementia, Vascular, Oligodendroglia

Published Open-Access

yes

Recommended Citation

Thorp, Edward B; Filipp, Mallory; Dima, Maria; et al., "CCR2+ Monocytes Promote White Matter Injury and Cognitive Dysfunction After Myocardial Infarction" (2024). Faculty, Staff and Student Publications. 5522.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5522