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Updated: Oct 19, 2025
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Systemic macrophage depletion attenuates infarct size in an experimental mouse model of stroke
Seung-Won Lee1, Dong-Jun Song2, Han-Seung Ryu1
1Department of Neurosurgery, Chonnam National University Hospital and Medical School, Gwangju, Korea.
Objective:
Macrophages have been shown to play important roles in various pathophysiological processes of the central nervous system via neuroinflammation, leading to an increased interest in macrophage biology. Circulating blood monocytes are among the first cells to infiltrate the brain after ischemic stroke; however, the role of innate immune cells such as monocytes and macrophages remains to be elucidated. Here, we investigated the association between blood monocytes and infarct size following ischemic stroke.
Methods:
We induced stroke using a focal ischemia mouse model through middle cerebral artery suture occlusion. To deplete circulating blood monocytes, clodronate was injected intraperitoneally 24 h before the surgery. Animals were sacrificed at specified time points, and the infarct size and mRNA expression were then measured.
Results:
The clodronate-injected mice showed significantly smaller infarct size than the control mice. Immunohistochemical staining revealed that monocyte depletion significantly blocked the infiltration of macrophages and microglia. The mRNA expression levels of macrophage and microglia markers were higher in the left infarcted brain than in the right non-infarcted brain.
Conclusions:
In summary, monocyte depletion reduced the infarct size and mitigated neurological deficits in mice following ischemic stroke, likely by blocking the infiltration of inflammatory cells such as macrophages and microglia.
Insights
Depleting circulating monocytes in mice significantly reduced brain infarct size after ischemic stroke. This suggests targeting these innate immune cells may be a promising therapeutic strategy for stroke recovery.
Area of Science:
- Neuroscience
- Immunology
- Pathophysiology
Background:
- Macrophages play key roles in central nervous system neuroinflammation.
- Monocytes are early responders infiltrating the brain post-ischemic stroke.
- The specific role of monocytes and macrophages in stroke pathophysiology requires further elucidation.
Purpose of the Study:
- To investigate the association between blood monocytes and infarct size following ischemic stroke.
- To determine the impact of monocyte depletion on brain injury after stroke.
Main Methods:
- A focal ischemia mouse model was established using middle cerebral artery suture occlusion.
- Circulating monocytes were depleted using intraperitoneal clodronate injection 24 hours prior to stroke induction.
- Infarct size and mRNA expression of immune cell markers were measured post-stroke.
Main Results:
- Mice with monocyte depletion exhibited significantly smaller infarct volumes compared to control groups.
- Immunohistochemistry confirmed that monocyte depletion inhibited the infiltration of macrophages and microglia into the brain.
- Elevated mRNA expression of macrophage and microglia markers was observed in the infarcted brain hemisphere.
Conclusions:
- Monocyte depletion effectively reduced infarct size and neurological deficits in a mouse model of ischemic stroke.
- The protective effect is likely mediated by blocking the infiltration of inflammatory cells like macrophages and microglia.
- Targeting blood monocytes presents a potential therapeutic avenue for mitigating ischemic stroke injury.
