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Related Experiment Video

Updated: Jul 4, 2026

Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
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Repopulating Microglia Suppress Peripheral Immune Cell Infiltration to Promote Poststroke Recovery.

Ligen Shi1,2,3, Lingxiao Lu1,3, Jun Hu1

  • 1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

CNS Neuroscience & Therapeutics
|September 11, 2025
PubMed
Summary

Transiently depleting and repopulating microglia after ischemic stroke reshapes the immune environment, promoting neurofunctional recovery. This approach enhances brain repair and functional outcomes post-stroke.

Keywords:
PLX5622immunomodulationneuroinflammationreplenished microglia

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Area of Science:

  • Neuroscience
  • Immunology
  • Regenerative Medicine

Background:

  • Sustained neuroinflammation after ischemic stroke hinders tissue repair and functional recovery.
  • Novel therapeutic strategies are needed to suppress inflammation and promote neurorestoration.

Purpose of the Study:

  • To investigate the effects of transient microglia depletion and repopulation on the post-stroke immune microenvironment.
  • To assess the impact of this immunomodulatory strategy on neurological functional recovery.

Main Methods:

  • Utilized a microglia depletion-repopulation paradigm using PLX5622 in a post-ischemic stroke model.
  • Employed single-cell transcriptomics, behavioral testing, cytokine arrays, flow cytometry, and immunofluorescence.

Main Results:

  • PLX5622 administration promoted neurofunctional recovery by reshaping the immune microenvironment.
  • Repopulated microglia exhibited a more homeostatic phenotype, reducing pro-inflammatory states.
  • Observed suppressed T cell exhaustion, limited neutrophil differentiation, and promoted phagocytic macrophages, potentially driven by reduced chemokine production and enhanced blood-brain barrier integrity.

Conclusions:

  • Transient microglial depletion and repopulation facilitate neurological function recovery post-stroke.
  • This immunomodulatory strategy shows promise for enhancing functional recovery in ischemic brain injury.
  • The approach is clinically translatable for improving rehabilitation outcomes.