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.

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.

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