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Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
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Shh regulates M2 microglial polarization and fibrotic scar formation after ischemic stroke

Qinghuan Yang1, Peiran Jiang1, Hao Tang1

  • 1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Neurochemistry International
|September 22, 2024
PubMed
Abstract

Insights

Sonic Hedgehog (Shh) signaling regulates fibrotic scar formation and microglial polarization after ischemic stroke. This pathway impacts tissue repair and neurological recovery, offering potential therapeutic targets.

Area of Science:

  • Neuroscience
  • Immunology
  • Regenerative Medicine

Background:

  • Fibrotic scar formation impairs recovery after ischemic stroke.
  • Mechanisms of central nervous system (CNS) fibrosis are poorly understood.
  • Microglia's role in CNS fibrosis and the Sonic Hedgehog (Shh) pathway's impact require investigation.

Purpose of the Study:

  • To investigate if Shh regulates fibrotic scar formation post-ischemic stroke.
  • To elucidate the underlying mechanisms of Shh in CNS fibrosis.
  • To explore Shh's interaction with microglial polarization.

Main Methods:

  • In vivo and in vitro manipulation of Shh expression in mouse models and cell cultures.
  • Analysis of Shh expression in stroke patients and MCAO/R mice.
  • Assessment of microglial polarization and fibroblast activation.

Main Results:

  • Shh was upregulated in stroke patients and MCAO/R mice, correlating with scar formation and M2 microglial polarization.
  • Shh knockdown reduced scarring and M2 polarization but worsened neurological deficits.
  • In vitro, Shh modulation affected microglial polarization and expression of TGFβ1 and PDGFA.

Conclusions:

  • Shh signaling plays a key role in regulating M2 microglial polarization.
  • Shh influences fibrotic scar formation following cerebral ischemia.
  • Targeting Shh may offer a novel therapeutic strategy for stroke recovery.
Keywords:
Fibrotic scarIschemic strokeMicrogliaShh

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