Related Experiment Video
Updated: Sep 21, 2025
Assessing Microglial Phagocytosis of Myelin Debris in vitro Under Repeated Magnetic Stimulation
Published on: June 17, 2025
Delayed Infiltration of Peripheral Monocyte Contributes to Phagocytosis and Transneuronal Degeneration in Chronic
Keun Woo Park1,2, Hyunwoo Ju1, Il-Doo Kim1
1Burke Neurological Institute, White Plains, NY (K.W.P., H.J., I.-d.K., Y.G., S.C.).
Background:
Mononuclear phagocytes, including monocyte-derived macrophages (MDMs) and microglia, contribute to infarct development as well as tissue repair in the postischemic brain. Here, we identify the origin and function of MDMs in the brain during poststroke repair processes.
Methods:
Adult mice were subjected to transient middle cerebral artery occlusion. Longitudinal brain atrophy and secondary degeneration were evaluated during acute to recovery phases of stroke. Adoptive transfer of GFP+ splenocytes into asplenic mice was used to distinguish MDMs from resident microglia. Fluorescence beads were injected into stroked animals to examine phagocytic function.
Results:
Progressive atrophy and neuronal degeneration in remote regions were observed in chronic stroke, which also was accompanied by MDM infiltration into the ipsilateral hemisphere. Compared with microglia, MDMs had significantly higher phagocytic activity. MDM trafficking and phagocytosis was spatiotemporally regulated with acute and prolonged infiltration into infarcted tissue, as well as delayed entry in remote areas such as the thalamus and substantia nigra.
Conclusions:
The stepwise and long-lasting involvement of MDMs at multiple poststroke stages shows that MDMs have a role in progressive stroke-induced injury and repair processes. These findings suggest that manipulating monocyte entry at different stroke stages may be an effective immune-based strategy to limit injury propagation in chronic stroke.
Insights
Monocyte-derived macrophages (MDMs) infiltrate the brain after stroke, exhibiting higher phagocytic activity than microglia and contributing to both injury and repair. Targeting MDM entry may offer a novel immune-based therapeutic strategy for chronic stroke.
Area of Science:
- Neuroscience
- Immunology
- Stroke Research
Background:
- Mononuclear phagocytes, including monocyte-derived macrophages (MDMs) and microglia, play dual roles in post-stroke brain injury and repair.
- Understanding the specific contributions of MDMs is crucial for developing effective stroke therapies.
Purpose of the Study:
- To investigate the origin and function of monocyte-derived macrophages (MDMs) in the brain during post-stroke repair.
- To differentiate MDM roles from resident microglia in the context of ischemic stroke.
Main Methods:
- Adult mice underwent transient middle cerebral artery occlusion to model stroke.
- Adoptive transfer of GFP+ splenocytes distinguished MDMs from microglia.
- Phagocytic activity was assessed using fluorescence beads.
Main Results:
- Monocyte-derived macrophages (MDMs) infiltrated the ipsilateral hemisphere during chronic stroke, showing progressive atrophy and neuronal degeneration.
- MDMs demonstrated significantly higher phagocytic activity compared to microglia.
- MDM infiltration and phagocytosis were spatiotemporally regulated, occurring acutely in infarcts and delayed in remote areas.
Conclusions:
- Monocyte-derived macrophages (MDMs) are involved in progressive stroke-induced injury and repair across multiple stages.
- Targeting monocyte infiltration at different stroke phases could be a viable immune-based strategy to mitigate chronic stroke injury.
Related Concept Videos
01:38Inflammation
01:15Neurogenesis and Regeneration of Nervous Tissue