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Updated: Apr 29, 2026
Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
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.
Abstract:
Pericytes are located on the abluminal side of endothelial cells lining the microvasculature in all organs. They have been identified as multipotent progenitor cells in several tissues of the body including the human brain. New evidence suggests that pericytes contribute to tissue repair, but their role in the injured brain is largely unknown. Here, we investigate the role of pericytes in ischemic stroke. Using a pericyte-reporter mouse model, we provide unique evidence that regulator of G-protein signaling 5 expressing cells are activated pericytes that leave the blood vessel wall, proliferate and give rise to microglial cells after ischemic brain injury. Consistently, we show that activated pericytes express microglial markers in human stroke brain tissue. We demonstrate that human brain-derived pericytes adopt a microglial phenotype and upregulate mRNA specific for activated microglial cells under hypoxic conditions in vitro. Our study indicates that the vasculature is a novel source of inflammatory cells with a microglial phenotype in brain ischemia and hence identifies pericytes as an important new target for the development of future stroke therapies.
Insights
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.
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.
