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Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Microglia activation in sepsis: a case-control study
Afina W Lemstra1, Jacqueline C M Groen in't Woud, Jeroen J M Hoozemans
1Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands. a.w.lemstra@amc.uva.nl
Background:
Infection induces an acute phase response that is accompanied by non-specific symptoms collectively named sickness behavior. Recent observations suggest that microglial cells play a role in mediating behavioral changes in systemic infections. In animal models for sepsis it has been shown that after inducing lipopolysaccharide, LPS, microglia in the brain were activated. The aim of this study was to investigate whether activation of microglia can be detected in patients who died of sepsis.
Methods:
In a case-control study brain tissue of 13 patients who died with sepsis was compared with that of 17 controls. Activated microglia were identified by expression of MHC-class II antigens and CD68. Microglia activation was analyzed by a semiquantitative score combining both the number of the immunoreactive cells and their morphology.
Results:
In patients who died with sepsis there was a significant increase in activated microglia in the grey matter when stained with CD68 compared to controls. This effect was independent of the effect of age.
Conclusion:
This study shows for the first time in human brain tissue an association between a systemic infection and activation of microglia in the brain. Activated microglia during sepsis could play a role in behavioral changes associated with systemic infection.
Insights
Sepsis infection activates brain microglia in deceased patients, suggesting a role in sickness behavior. This study confirms microglial activation in human sepsis brains, linking infection to neurological changes.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Infections trigger the acute phase response and sickness behavior.
- Microglial cells are implicated in mediating behavioral changes during systemic infections.
- Animal models show microglial activation in the brain following lipopolysaccharide (LPS) induction in sepsis.
Purpose of the Study:
- To investigate microglial activation in the brains of patients who died from sepsis.
- To determine if observed microglial activation in animal models translates to human sepsis cases.
Main Methods:
- A case-control study comparing brain tissue from 13 sepsis patients and 17 controls.
- Identification of activated microglia via MHC-class II antigens and CD68 expression.
- Semiquantitative scoring of microglia activation based on cell number and morphology.
Main Results:
- Significant increase in CD68-positive activated microglia in the grey matter of sepsis patients compared to controls.
- Microglial activation was observed independently of the patients' age.
- Demonstrated a clear link between sepsis and microglial activation in human brain tissue.
Conclusions:
- First evidence of microglial activation in human brain tissue associated with systemic sepsis.
- Activated microglia in sepsis may contribute to the associated behavioral changes.
- Highlights the brain's involvement in the systemic response to infection.
