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Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
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Systemic infection and microglia activation: a prospective postmortem study in sepsis patients

D Westhoff1, J Y Engelen-Lee1, I C M Hoogland1

  • 11Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.

Immunity & Ageing : I & A
|August 7, 2019
PubMed
Abstract

Insights

Severe systemic inflammation during septic shock increases CD-68 positive microglia in the brain, particularly in the hippocampus, putamen, and cerebellum. This neuroinflammation was not linked to anticholinergic medication use.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Systemic infection and severe inflammation can cause long-term cognitive deficits and functional decline.
  • Neuroinflammation, characterized by microglial activation, is a potential mechanism linking systemic inflammation to cognitive impairment.
  • Anticholinergic medications may exacerbate these neuroinflammatory effects.

Purpose of the Study:

  • To investigate the neuroinflammatory response in patients with septic shock.
  • To determine if severe systemic inflammation leads to microglial activation in specific brain regions.
  • To explore the potential influence of anticholinergic medications on sepsis-induced neuroinflammation.

Main Methods:

  • Assessed microglial activation markers (MHC-II and CD-68) using immunohistochemistry.
  • Compared microglia counts in specific brain regions between patients with septic shock and control groups.
  • Correlated microglia counts with anticholinergic drug scores.

Main Results:

  • Patients with septic shock showed significantly higher CD-68 positive microglia in the hippocampus, putamen, and cerebellum compared to controls.
  • No significant difference in MHC-II positive microglia density was observed between sepsis and control groups.
  • Microglia counts did not consistently correlate with anticholinergic medication use.

Conclusions:

  • Severe systemic inflammation in fatal septic shock is associated with localized upregulation of CD-68 positive microglia.
  • Increased microglial activation was observed in the putamen, hippocampus, and cerebellum, indicating regional brain vulnerability.
  • The study did not find a link between microglial activation and anticholinergic drug burden in this patient cohort.
Keywords:
DeliriumMicrogliaNeuroinflammationSepsisSepsis associated encephalopathy

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