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Pro‐inflammatory activation of microglia in the brain of patients with sepsis
Author(s) -
Zrzavy T.,
Höftberger R.,
Berger T.,
Rauschka H.,
Butovsky O.,
Weiner H.,
Lassmann H.
Publication year - 2019
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12502
Subject(s) - microglia , inflammation , systemic inflammation , neuroinflammation , grey matter , immunology , white matter , medicine , central nervous system , pathology , biology , magnetic resonance imaging , radiology
Aims Experimental data suggest that systemic immune activation may create a pro‐inflammatory environment with microglia activation in the central nervous system in the absence of overt inflammation, which in turn may be deleterious in conditions of neurodegenerative disease. The extent to which this is relevant for the human brain is unknown. The central aim of this study is to provide an in‐depth characterization of the microglia and macrophage response to systemic inflammation. Methods We used recently described markers to characterize the origin and functional states of microglia/macrophages in white and grey matter in patients who died under septic conditions and compared it to those patients without systemic inflammation. Results We found pro‐inflammatory microglia activation in septic patients in the white matter, with very little activation in the grey matter. Using a specific marker for resident microglia ( TMEM 119), we found that parenchyma microglia were activated and that there was additional recruitment of perivascular macrophages. Pro‐inflammatory microglia activation occurred in the presence of homeostatic microglia cells. In contrast to inflammatory or ischaemic diseases of the brain, the anti‐inflammatory microglia markers CD 163 or CD 206 were not expressed in acute sepsis. Furthermore, we found pronounced upregulation of inducible nitric oxide synthase not only in microglia, but also in astrocytes and endothelial cells. Conclusion Our results demonstrate the pronounced effects of systemic inflammation on the human brain and have important implications for the selection of control populations for studies on microglia activation in human brain disease.