Functional heterogeneity of microglia and macrophages in the ischemic brain

• Autorzy: Kaminska B.
• Języki publikacji: EN

Abstrakty

EN

Microglia are myeloid cells residing in the central nervous system (CNS) that rapidly respond to signals originating in the injured or infected brain. Microglia respond differently to challenges and acquire different functional phenotypes with extremes: an inflammatory, detrimental M1 or immunosuppressive, cytoprotective M2 phenotype. Post‑ischemic inflammation plays a key role in secondary and delayed neuronal damage and death, and involves activation of microglia, perivascular and peripheral macrophages, that accumulate in the ischemic brain and contribute to disease. The molecular signature of myeloid cells in the inflammed brain, and specific roles of different populations are unclear. Lack of robust markers that differentiate microglia from macrophages makes it less feasible. We developed effective, flow cytometry‑based methods for sorting myeloid subpopulations that accumulate in the hemispheres of sham-operated and ischemic rats undergoing transient 90 min MCA (middle cerebral artery) occlusion. We analyzed transcriptomes of specific populations by RNAseq and evaluated their functional phenotypes. This analysis revealed a prevalence of inflammatory M1 microglia 1 day after MCAo and accumulation of M2-immunosuppressive macrophages 3–7 days after MCAo. Ablation of peripheral macrophages reduced abundance of M2 immunosuppressive, Arg1 expressing macrophages. Using immunofluorescence and confocal microscopy we demonstrated that with time Arg1+ macrophages lose their M2‑phenotype and become inflammatory iNos expressing cells. Moreover, we found that macrophages of perivascular space and meninges (defined by CD163+ staining) are a distinct myeloid subpopulation in the brain, and these cells proliferate and migrate to the ischemic parenchyma after MCAo. Altogether, we demonstrate distinct functional properties and transcriptional networks in brain macrophages, that suggests functional plasticity and distinctive functions in neuroinflammation and repair.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.46

Twórcy

autor

Kaminska B.

• Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland