Systemic infection and microglia activation: A prospective postmortem study in sepsis patients

D. Westhoff, J. Y. Engelen-Lee, I. C. M. Hoogland, E. M. A. Aronica, D. J. van Westerloo, D. van de Beek, W. A. van Gool

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Abstract

Background: Systemic infection is associated with long-term cognitive deficits and functional decline. In this study we hypothesized that severe systemic inflammation leads to a neuroinflammatory response that is characterized by microglial activation, and that these effects might be more pronounced in patients using medication with anticholinergic side-effects. Methods: Based on the results of a pilot study in 8 patients, we assessed the number of MHC-II and CD-68 positive cells by immunohistochemistry and compared the number of microglia in specific brain regions of 16 well-characterized patients with septic shock and 15 controls. Results: In the pilot study, patients with sepsis tended to have higher density of MHC-II and CD-68 positive microglia in the basal ganglia (putamen, caudate nucleus and globus pallidus) and of MHC-II positive microglia in the hippocampus. In the validation study, patients with sepsis had a significantly higher number of CD-68 positive cells in hippocampus (1.5 fold; p = 0.012), putamen (2.2 fold; p = 0.008) and cerebellum (2.5 fold; p = 0.011) than control patients. The density of MHC-II positive microglia was similar between sepsis and control groups. There was no consistent correlation between microglia counts and anti-cholinergic activity drugs score. Conclusion: In patients who die during septic shock, severe systemic inflammation is accompanied by localized and strong upregulation of CD-68 positive microglia, but not of MHC-II positive microglia. We identified regional differences in the brain with increased microglial activation in putamen, hippocampus and cerebellum.
Original languageEnglish
Article number18
JournalImmunity & ageing
Volume16
Issue number1
DOIs
Publication statusPublished - 30 Jul 2019
Externally publishedYes

Cite this

Westhoff, D., Engelen-Lee, J. Y., Hoogland, I. C. M., Aronica, E. M. A., van Westerloo, D. J., van de Beek, D., & van Gool, W. A. (2019). Systemic infection and microglia activation: A prospective postmortem study in sepsis patients. Immunity & ageing, 16(1), [18]. https://doi.org/10.1186/s12979-019-0158-7