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Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Increased expression of macrophage receptor with collagenous structure (MARCO) in mouse cortex following middle
Stuart A Milne1, Ailsa L McGregor, James McCulloch
1Astellas CNS in Edinburgh, The University of Edinburgh, UK. stuart.miline@ed.ac.uk
Abstract:
Ischaemia induces activation of resident microglia and infiltration of peripheral monocyte/macrophage cells into the central nervous system. The role of scavenger receptors, receptors critical to the recognition and clearance of cell debris, has not been investigated during cerebral ischaemia. MARCO is an inducible member of the scavenger receptor family unique to cells of monocytic lineage and is a cell surface marker that plays a critical role in the differentiation of monocytes to dendritic cells. To understand the role of MARCO in cerebral ischaemia, we investigated its expression in mice following middle cerebral artery (MCA) occlusion. No MARCO mRNA expression was observed in naive mouse brain. There was no significant increase in expression of MARCO mRNA following transient occlusion (60min) of the MCA at any time point up to 24 h. However, a significant, marked increase in MARCO mRNA expression was observed at 24 h in the cortex of mouse brains after a permanent occlusion of the MCA. The increased expression of MARCO mRNA at 24 h after prolonged ischaemia is consistent with its putative role in the clearance of debris and/or degenerating cells after severe ischaemia and supports previous publications showing the presence of dendritic cells around permanently occluded lesions.
Insights
Scavenger receptor MARCO expression increases in mouse brains after permanent cerebral ischemia, suggesting a role in clearing debris. This finding is linked to dendritic cell presence around lesions.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Cerebral ischemia triggers microglial activation and monocyte infiltration into the brain.
- Scavenger receptors are crucial for clearing cellular debris but their role in cerebral ischemia is unknown.
- MARCO, a scavenger receptor on monocytic cells, is involved in monocyte differentiation.
Purpose of the Study:
- To investigate the expression of MARCO in the mouse brain following middle cerebral artery (MCA) occlusion.
- To determine the role of MARCO in the context of cerebral ischemia and debris clearance.
Main Methods:
- Middle cerebral artery (MCA) occlusion was performed in mice to induce transient and permanent cerebral ischemia.
- MARCO mRNA expression was analyzed in brain tissue at various time points post-occlusion using quantitative methods.
Main Results:
- No MARCO mRNA was detected in naive mouse brains.
- Transient MCA occlusion did not significantly alter MARCO mRNA expression up to 24 hours.
- Permanent MCA occlusion led to a significant increase in MARCO mRNA expression in the cortex at 24 hours.
Conclusions:
- Increased MARCO mRNA expression after prolonged cerebral ischemia suggests its involvement in clearing degenerating cells and debris.
- The findings support the role of MARCO in the immune response to severe brain injury.
- This study highlights the potential role of MARCO in the context of dendritic cell presence around ischemic lesions.

