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Systemic inflammation attenuates the repair of damaged brains through reduced phagocytic activity of monocytes infiltrating the brain

Authors
Gaire, S | An, J  | Yang, H  | Lee, KA  | Dumre, M | Lee, EJ  | Park, SM  | Joe, EH
Citation
Molecular brain, 17(1). : 47-47, 2024
Journal Title
Molecular brain
ISSN
1756-6606
Abstract
In this study, we examined how systemic inflammation affects repair of brain injury. To this end, we created a brain-injury model by stereotaxic injection of ATP, a damage-associated molecular pattern component, into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). An analysis of magnetic resonance images showed that LPS-ip reduced the initial brain injury but slowed injury repair. An immunostaining analysis using the neuronal marker, NeuN, showed that LPS-ip delayed removal of dead/dying neurons, despite the fact that LPS-ip enhanced infiltration of monocytes, which serve to phagocytize dead cells/debris. Notably, infiltrating monocytes showed a widely scattered distribution. Bulk RNAseq analyses showed that LPS-ip decreased expression of genes associated with phagocytosis, with PCR and immunostaining of injured brains confirming reduced levels of Cd68 and Clec7a, markers of phagocytic activity, in monocytes. Collectively, these results suggest that systemic inflammation affects properties of blood monocytes as well as brain cells, resulting in delay in clearing damaged cells and activating repair processes.
Keywords

MeSH

DOI
10.1186/s13041-024-01116-3
PMID
39075534
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Journal Papers > Research Organization > Brain Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Brain Science
Ajou Authors
AN, JIAWEI  |  박, 상면  |  양, 해걸  |  이, 건아  |  이, 은정  |  조, 은혜
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