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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
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Microglia in the aged brain develop a hypoactive molecular phenotype after surgery.

Zhuoran Yin1,2, Anna K Leonard3, Carl M Porto3

  • 1Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.

Journal of Neuroinflammation
|December 19, 2024
PubMed
Summary
This summary is machine-generated.

Surgery transiently suppresses microglial pro-inflammatory responses in aged mice, challenging assumptions about post-operative brain inflammation. This study reveals a homeostatic shift in microglia, particularly in older animals, following surgical procedures.

Keywords:
AgingMicrogliaNeuroinflammationSurgery

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Area of Science:

  • Neuroscience
  • Immunology
  • Aging Research

Background:

  • Microglia are key brain immune cells involved in CNS homeostasis.
  • Dysregulated microglial activity can contribute to neuroinflammation and neurodegeneration.
  • Post-operative cognitive deficits are linked to inflammation, with microglia implicated via morphological changes.

Purpose of the Study:

  • To investigate the impact of surgery on the microglial transcriptome.
  • To test the hypothesis that surgery induces an age-dependent pro-inflammatory microglial phenotype.

Main Methods:

  • Abdominal laparotomy in young and aged mice, with sacrifice at 6 and 48 hours post-surgery.
  • Cytokine analysis (ELISA), Iba1 immunohistochemistry, and microglial isolation via FACS.
  • Transcriptome analysis using qPCR and RNA sequencing.

Main Results:

  • Surgery elevated plasma cytokines; CCL2 increased in the brain, more so in aged mice.
  • Microglia adopted a homeostatic molecular phenotype post-surgery, particularly in aged mice.
  • Surgery upregulated genes typically downregulated in neurodegenerative microglia (MGnD/DAM), a transient effect resolving by 48 hours.

Conclusions:

  • Anesthesia and surgery induce transient pro-inflammatory changes peripherally but a homeostatic microglial phenotype centrally.
  • This homeostatic microglial response is more pronounced in aged mice.
  • Findings challenge the notion that surgery consistently activates microglia in the aged brain.