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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

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From Tim4 to ischemic stroke: a mitochondrial pathway driving microglial M1 polarization

Zhinan Ye1, Yingying Jin2, Hao Xu1

  • 1Department of Neurology, Taizhou Municipal Hospital (Taizhou University Affiliated Municipal Hospital), School of Medicine, Taizhou University, Taizhou, China.

Brain Research
|January 3, 2026
PubMed

Insights

T-cell immunoglobulin and mucin domain 4 (Tim4) promotes M1 microglial polarization and mitochondrial dysfunction in ischemic stroke. Targeting Tim4 offers a potential therapeutic strategy for stroke by modulating microglial responses.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia dysfunction is a key factor in ischemic stroke pathology.
  • T-cell immunoglobulin and mucin domain 4 (Tim4) is implicated in microglial function.

Purpose of the Study:

  • To investigate the role of Tim4 in microglial polarization and mitochondrial dynamics following ischemic stroke.
  • To evaluate Tim4 as a potential therapeutic target for ischemic stroke.

Main Methods:

  • Ischemic stroke was modeled using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) in rodents.
  • Assessed infarct volume, neurological deficits, apoptosis, microglial polarization (M1/M2), Tim4 expression, mitochondrial fission proteins (MFF, Drp1), mitochondrial membrane potential (MMP), and reactive oxygen species (ROS).

Main Results:

  • MCAO induced increased infarct volume, neurological deficits, apoptosis, and M1 microglia.
  • Tim4 upregulation correlated with increased ROS, enhanced mitochondrial fission (MFF, Drp1), and reduced MMP in microglia.
  • Tim4 knockdown reversed these effects, while Drp1 overexpression partially offset Tim4 knockdown's impact on microglial polarization.

Conclusions:

  • Tim4 promotes M1 microglial polarization and mitochondrial fission in ischemic stroke.
  • Tim4 regulates microglial M1 polarization through mitochondrial pathways.
  • Tim4 represents a potential therapeutic target for treating ischemic stroke.
Keywords:
Ischemic strokeM1 polarizationMicrogliaMitochondriaT-cell immunoglobulin and mucin domain 4

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