Related Experiment Video
Updated: Jan 17, 2026
Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
Injury to repair: Functions of microglia and monocyte-derived cells in ischemic stroke
Ryan Martynowicz1, David P Sullivan2, Ayush Batra3
1Ken and Ruth Davee Department of Neurology,Northwestern University Feinberg School of Medicine, Chicago, IL USA.
Introduction:
Microglia, the central nervous system's resident immune cells, play a complex role in acute ischemic stroke (AIS), contributing to both neuroprotection and secondary neurologic injury. After ischemic injury, microglia activate and adopt a diverse range of phenotypes, from extremes of pro-inflammatory to anti-inflammatory microglia. Coinciding with microglial activation, AIS triggers infiltration of monocytes, which transform into monocyte-derived cells (MdCs) within the ischemic microenvironment. MdCs display many overlapping characteristics with microglia, complicating their identification and role in recovery.
Methods:
This narrative review synthesizes current basic and translational research examining the heterogeneity and interplay of microglia and MdCs in response to AIS. Relevant literature was identified through a comprehensive search of the PubMed database, inclusive of studies published through June 2025.
Results And Conclusions:
Anti-inflammatory microglial phenotypes promote neuronal survival, phagocytosis of necrotic debris, and blood-brain barrier repair. Pro-inflammatory microglial phenotypes, conversely, exacerbate injury through excitotoxicity, cytokine release, and vascular disruption. Initially, MdCs adopt a neuroprotective, reparative microglia-like role by phagocytizing debris and supporting repair but later shift to a pro-inflammatory phenotype, driving secondary damage. The dynamic interaction between microglia and MdCs is crucial for stroke recovery, with microglia and MdCs initially aiding in tissue repair and angiogenesis while subsequently amplifying secondary injury through pro-inflammatory phenotypes. Although various biomarkers have been proposed to differentiate microglia from MdCs and predict stroke outcomes, none have been clinically validated. Further studies are needed to identify reliable biomarkers for these distinct cell types and develop strategies to minimize secondary injury without impairing recovery after stroke.
Insights
Microglia and monocyte-derived cells (MdCs) have dual roles in acute ischemic stroke (AIS), initially aiding repair but later causing secondary injury. Understanding their complex interplay is key to improving stroke recovery and developing targeted therapies.
Area of Science:
- Neuroscience
- Immunology
- Stroke Research
Background:
- Microglia, the brain's immune cells, have complex roles in acute ischemic stroke (AIS), mediating both protection and injury.
- AIS activates microglia into diverse phenotypes, while infiltrating monocytes form monocyte-derived cells (MdCs) with overlapping characteristics.
Purpose of the Study:
- To review the heterogeneity and interplay of microglia and monocyte-derived cells in response to AIS.
- To synthesize current research on their roles in neuroprotection and secondary injury.
Main Methods:
- A narrative review of basic and translational research.
- Literature search of the PubMed database up to June 2025.
Main Results:
- Anti-inflammatory microglia promote neuronal survival and repair; pro-inflammatory phenotypes exacerbate injury.
- Monocyte-derived cells initially support repair but later contribute to secondary damage.
- The dynamic interaction between microglia and MdCs influences stroke recovery and secondary injury.
Conclusions:
- Microglia and MdCs initially aid tissue repair and angiogenesis but can amplify secondary injury.
- Reliable biomarkers to differentiate these cells and predict outcomes are lacking.
- Further research is needed to identify biomarkers and develop strategies to mitigate secondary injury without hindering recovery.
