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Updated: Aug 4, 2026

Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
A previous hemorrhagic stroke protects against a subsequent stroke via microglia alternative polarization
Shin-Shin Lee1, Li Pang1, Yin Cheng1
1Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
Abstract:
Microglia in hemorrhagic stroke contribute to both acute-phase exacerbation and late-phase attenuation of injury. Here, by using the mouse model, we reported that the shift in polarization of microglia from M1 to M2 phenotype could be altered by a past 'mini' stroke, resulting in better neurological function recovery, faster attenuation of lesion volume, and better survival. In mice with a previous stroke, M2 predominance appeared markedly in advance compared to mice without a previous stroke. Mechanistically, the RBC-mediated M2 polarization of microglia was synergistically enhanced by T cells: microglia cocultured with RBCs alone resulted in mild alterations to M2 markers, whereas in the presence of T cells, they expressed an early and sustained M2 response. These results suggest that by harnessing the microglia-mediated M2 polarization response, we could help mitigate devastating sequelae before a prospective hemorrhagic stroke even happens.
Insights
A prior 'mini' stroke primes microglia to an M2 phenotype, enhancing recovery and survival after hemorrhagic stroke. This protective effect is boosted by T cells, suggesting a novel therapeutic strategy.
Area of Science:
- Neuroscience
- Immunology
- Stroke Research
Background:
- Microglia play a dual role in hemorrhagic stroke, causing initial damage and later aiding recovery.
- Understanding microglia polarization is key to developing effective stroke treatments.
Purpose of the Study:
- To investigate how a prior ischemic stroke influences microglial response in a subsequent hemorrhagic stroke model.
- To elucidate the mechanisms behind T cell and red blood cell (RBC) involvement in microglial polarization.
Main Methods:
- Utilized a mouse model of hemorrhagic stroke.
- Analyzed microglial polarization (M1 to M2 phenotype) in mice with and without a prior ischemic stroke.
- Investigated the role of T cells and RBCs in microglial M2 polarization through co-culture experiments.
Main Results:
- A prior ischemic stroke significantly accelerated the shift of microglia towards the M2 phenotype in a subsequent hemorrhagic stroke.
- Mice with a prior stroke showed improved neurological function, reduced lesion volume, and better survival rates.
- T cells synergistically enhanced RBC-mediated M2 polarization of microglia, leading to an earlier and sustained M2 response.
Conclusions:
- Preconditioning with a minor stroke can reprogram microglia, offering protection against severe hemorrhagic stroke outcomes.
- The synergistic interaction between T cells and RBCs is crucial for promoting beneficial M2 microglial polarization.
- Targeting microglial M2 polarization presents a promising pre-emptive therapeutic avenue for mitigating hemorrhagic stroke sequelae.
Related Concept Videos
Ischemic Stroke ll: Pathophysiology
Hemorrhagic Stroke l: Introduction
Hemorrhagic Stroke ll: Pathophysiology

