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01-04-2018 | Original Paper

Distinguishing features of microglia- and monocyte-derived macrophages after stroke

Authors: Golo Kronenberg, Ria Uhlemann, Nadine Richter, Friederike Klempin, Stephanie Wegner, Lilian Staerck, Susanne Wolf, Wolfgang Uckert, Helmut Kettenmann, Matthias Endres, Karen Gertz

Published in: Acta Neuropathologica | Issue 4/2018

Abstract

After stroke, macrophages in the ischemic brain may be derived from either resident microglia or infiltrating monocytes. Using bone marrow (BM)-chimerism and dual-reporter transgenic fate mapping, we here set out to delimit the responses of either cell type to mild brain ischemia in a mouse model of 30 min transient middle cerebral artery occlusion (MCAo). A discriminatory analysis of gene expression at 7 days post-event yielded 472 transcripts predominantly or exclusively expressed in blood-derived macrophages as well as 970 transcripts for microglia. The differentially regulated genes were further collated with oligodendrocyte, astrocyte, and neuron transcriptomes, resulting in a dataset of microglia- and monocyte-specific genes in the ischemic brain. Functional categories significantly enriched in monocytes included migration, proliferation, and calcium signaling, indicative of strong activation. Whole-cell patch-clamp analysis further confirmed this highly activated state by demonstrating delayed outward K⁺ currents selectively in invading cells. Although both cell types displayed a mixture of known phenotypes pointing to the significance of ‘intermediate states’ in vivo, blood-derived macrophages were generally more skewed toward an M2 neuroprotective phenotype. Finally, we found that decreased engraftment of blood-borne cells in the ischemic brain of chimeras reconstituted with BM from Selplg^−/− mice resulted in increased lesions at 7 days and worse post-stroke sensorimotor performance. In aggregate, our study establishes crucial differences in activation state between resident microglia and invading macrophages after stroke and identifies unique genomic signatures for either cell type.

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Title: Distinguishing features of microglia- and monocyte-derived macrophages after stroke
Authors: Golo Kronenberg
Ria Uhlemann
Nadine Richter
Friederike Klempin
Stephanie Wegner
Lilian Staerck
Susanne Wolf
Wolfgang Uckert
Helmut Kettenmann
Matthias Endres
Karen Gertz
Publication date: 01-04-2018
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 4/2018
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-017-1795-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Distinguishing features of microglia- and monocyte-derived macrophages after stroke

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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