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Brain pericytes acquire a microglial phenotype after stroke.

Ilknur Özen1, Tomas Deierborg, Kenichi Miharada

  • 1Translational Neurology Group, Department of Clinical Science, Wallenberg Neuroscience Center, Lund University, 22184, Lund, Sweden.

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Pericytes in the brain transform into microglial cells following ischemic stroke. This discovery reveals pericytes as a new source of inflammatory cells and a potential therapeutic target for stroke treatment.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Vascular Biology

Background:

  • Pericytes are crucial cells in microvasculature, identified as multipotent progenitors in the human brain.
  • Their role in brain tissue repair, particularly after injury, remains largely unexplored.
  • Understanding pericyte behavior in ischemic stroke is critical for developing new therapies.

Purpose of the Study:

  • To investigate the function of pericytes in the context of ischemic brain injury.
  • To determine if pericytes contribute to the cellular response following stroke.
  • To identify pericytes as a potential cellular source for inflammatory cells in the injured brain.

Main Methods:

  • Utilized a pericyte-reporter mouse model to track pericyte behavior after induced ischemic injury.
  • Analyzed brain tissue from both mice and human stroke patients.
  • Cultured human brain-derived pericytes under hypoxic conditions in vitro.

Main Results:

  • Regulator of G-protein signaling 5 (RGS5) expressing cells were identified as activated pericytes.
  • Activated pericytes were observed to migrate from the vessel wall, proliferate, and differentiate into microglial cells post-stroke.
  • Human stroke brain tissue showed activated pericytes expressing microglial markers.
  • In vitro studies confirmed human pericytes adopting a microglial phenotype under hypoxia.

Conclusions:

  • The brain vasculature serves as a novel source of inflammatory cells with a microglial phenotype during ischemia.
  • Activated pericytes are a significant contributor to the cellular response following ischemic stroke.
  • Pericytes represent a promising new therapeutic target for stroke treatment strategies.