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

Publisher: BioMed Central Country of Publication: England NLM ID: 101468876 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-6606 (Electronic) Linking ISSN: 17566606 NLM ISO Abbreviation: Mol Brain Subsets: MEDLINE

Original Publication: London : BioMed Central

Phagocytosis*/drug effects ; Monocytes*/metabolism ; Inflammation*/pathology ; Brain*/pathology ; Mice, Inbred C57BL* ; Lipopolysaccharides*/pharmacology; Animals ; Male ; Brain Injuries/pathology ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Neurons/metabolism ; Neurons/pathology ; Neurons/drug effects ; Lectins, C-Type/metabolism ; Wound Healing ; Mice ; Adenosine Triphosphate/metabolism ; CD68 Molecule

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.
(© 2024. The Author(s).)

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NRF-M-20230A0403-00173 PM Korean government; NRF-2019R1A5A2026045 KOSEF through the center for convergence research of neurological disorders

Keywords: Brain injury; Monocytes; Phagocytosis; Repair; Systemic inflammation

0 (Lipopolysaccharides)
0 (Antigens, CD)
0 (Antigens, Differentiation, Myelomonocytic)
0 (Lectins, C-Type)
0 (CD68 protein, mouse)
8L70Q75FXE (Adenosine Triphosphate)
0 (CD68 Molecule)

Date Created: 20240729 Date Completed: 20240730 Latest Revision: 20240801

20250114

PMC11288066

10.1186/s13041-024-01116-3

39075534