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KMID : 1005420210230040304
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Journal of Cerebrovascular and Endovascular Neurosurgery
2021 Volume.23 No. 4 p.304 ~ p.313
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Systemic macrophage depletion attenuates infarct size in an experimental mouse model of stroke
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Lee Seung-Won
Song Dong-Jun
Ryu Han-Seung
Kim You-Sub
Kim Tae-Sun
Joo Sung-Pil
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Abstract
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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.
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KEYWORD
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Cerebral ischemia, Clodronate, Macrophages, Microglia, Infarction
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