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Updated: Jun 22, 2026

Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
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Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury

Published on: September 4, 2013

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C5aR1+ microglia exacerbate neuroinflammation and cerebral edema in acute brain injury

Jinpeng Zhou1, Shuoyao Ma1, Dayun Feng1

  • 1Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.

Neuron
|November 19, 2025
PubMed

Insights

A novel microglial subtype expressing C5a receptor 1 (C5aR1) drives brain swelling after injury. Targeting C5aR1 reduces cerebral edema in traumatic brain injury and intracerebral hemorrhage models.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Microglia are key immune cells in the brain, responding rapidly to injury.
  • Neuroinflammation and cerebral edema are critical factors in stroke and traumatic brain injury (TBI) outcomes.
  • Microglial heterogeneity presents challenges for targeted therapies.

Purpose of the Study:

  • To identify and characterize novel microglial subtypes involved in acute brain injury.
  • To investigate the role of C5a receptor 1 (C5aR1) in microglial-mediated neuroinflammation and cerebral edema.
  • To evaluate C5aR1 as a potential therapeutic target for acute brain injury.

Main Methods:

  • Analysis of human cerebral edema tissue from TBI and intracerebral hemorrhage (ICH) patients.
  • Preclinical models of TBI and ICH to study microglial responses.
  • Genetic ablation of the C5ar1 gene in microglia.
  • Pharmacological inhibition of C5aR1 using an FDA-approved antagonist.

Main Results:

  • A distinct microglial subtype expressing C5aR1 was identified in human cerebral edema.
  • C5aR1+ microglia amplify neuroinflammation, promote neurotoxic astrocyte polarization, and recruit neutrophils in preclinical models.
  • Genetic or pharmacological inhibition of C5aR1 significantly reduced cerebral edema in TBI and ICH models.
  • C5aR1+ microglia were found to engage with both local and peripherally derived C5a.

Conclusions:

  • C5aR1+ microglia represent a critical driver of cerebral edema following acute brain injury.
  • Targeting C5aR1 offers a promising therapeutic strategy to mitigate brain swelling and improve outcomes in TBI and ICH.
Keywords:
C5aR1(+) microgliacerebral edemamicroglial heterogeneityneurotoxic astrocytesneutrophils recruitment

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