Functional differences between microglia and monocytes after ischemic stroke

Journal of Neuroinflammation

Louise D. McCullough¹  Evan R. Jellison²  Rajkumar Verma¹  Joshua Crapser¹  Jeremy M. Grenier¹  Anita R. Patel¹  Rodney M. Ritzel¹ 

[1] Department of Neurology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington 06030, CT, USA;Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA

关键词: Phagocytosis;    Inflammation;    Stroke;    Monocytes;    Microglia;   

Others  :  1221970
DOI  :  10.1186/s12974-015-0329-1

 received in 2015-03-03, accepted in 2015-05-20,  发布年份 2015

【 摘 要 】

Background

The brain’s initial innate response to stroke is primarily mediated by microglia, the resident macrophage of the CNS. However, as early as 4 h after stroke, the blood–brain barrier is compromised and monocyte infiltration occurs. The lack of discriminating markers between these two myeloid populations has led many studies to generate conclusions based on the grouping of these two populations. A growing body of evidence now supports the distinct roles played by microglia and monocytes in many disease models.

Methods

Using a flow cytometry approach, combined with ex-vivo functional assays, we were able to distinguish microglia from monocytes using the relative expression of CD45 and assess the function of each cell type following stroke over the course of 7 days.

Results

We found that at 72 h after a 90-min middle cerebral artery occlusion (MCAO), microglia populations decrease whereas monocytes significantly increase in the stroke brain compared to sham. After stroke, BRDU incorporation into monocytes in the bone marrow increased. After recruitment to the ischemic brain, these monocytes accounted for nearly all BRDU-positive macrophages. Inflammatory activity peaked at 72 h. Microglia produced relatively higher reactive oxygen species and TNF, whereas monocytes were the predominant IL-1β producer. Although microglia showed enhanced phagocytic activity after stroke, monocytes had significantly higher phagocytic capacity at 72 h. Interestingly, we found a positive correlation between TNF expression levels and phagocytic activity of microglia after stroke.

Conclusions

In summary, the resident microglia population is vulnerable to the effects of severe ischemia, show compromised cell cycle progression, and adopt a largely pro-inflammatory phenotype after stroke. Infiltrating monocytes are primarily involved with early debris clearance of dying cells. These findings suggest that the early wave of infiltrating monocytes may be beneficial to stroke repair and future therapies aimed at mitigating microglia cell death may prove more effective than attempting to elicit targeted anti-inflammatory responses from damaged cells.

【 授权许可】

   
2015 Ritzel et al.

【 图 表 】

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