CCR2-dependent monocytes/macrophages exacerbate acute brain injury but promote functional recovery after ischemic stroke in mice.

Theranostics
Weirong FangHeng Zhao

Abstract

Rationale: Peripheral blood monocytes are recruited into the ischemic brain and transform into macrophages after stroke. Nevertheless, the exact role of CCR2-dependent monocytes/macrophages in brain injury after stroke remains elusive. Methods: We used CCR2 knockout (KO) mice and the CCR2 pharmacological inhibitor, propagermanium (PG), to address the role of CCR2-dependent monocytes/macrophages in the acute stage and neurological functional recovery after middle cerebral artery (MCA) occlusion and reperfusion. Results: CCR2 KO resulted in smaller infarct size and lower mortality than in wild type (WT) mice, when measured 3 days after stroke. However, from 5 to 28 days after stroke, the KO mice had higher mortality and showed no obvious neurological functional recovery. In addition, WT mice treated with PG had similar stroke outcomes compared with CCR2 KO, as measured by T2 weighted MRI. Flow cytometry and real-time PCR analyses suggest that monocyte-derived macrophages (MoDMs) in the stroke brains mainly polarized to pro-inflammatory macrophages at the early stage, but gradually switched to anti-inflammatory macrophages at 7 days after stroke. In addition, adoptive transfer of anti-inflammatory macrophages into CCR2 KO mice at ...Continue Reading

Citations

Mar 22, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yan WangHeng Zhao
Feb 20, 2019·Acta Neuropathologica Communications·Abhijit NirwaneYao Yao
Mar 11, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Jordi PedragosaAnna M Planas
Jul 12, 2019·Journal of Neuroinflammation·Richard L JayarajGary A Rosenberg
Oct 4, 2020·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Dong HanYan Gao
Aug 8, 2020·Frontiers in Neurology·Michelle R DickersonPamela J VandeVord
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Fuyou GuoShixiong Lei
Dec 21, 2020·Trends in Pharmacological Sciences·Shenpeng R ZhangChristopher G Sobey
Jan 20, 2021·Nature Neuroscience·Panagiotis MastorakosDorian B McGavern
Nov 17, 2020·Frontiers in Neurology·Joohyun ParkJong Eun Lee
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Feb 26, 2021·Proceedings of the National Academy of Sciences of the United States of America·Lili XieLarry Benowitz
Apr 6, 2021·Molecular Neurobiology·Kanika VasudevaAnjana Munshi
Jul 1, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Fangfang FanXiaobo Wang
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Oct 2, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Dilidaer MisilimuYanqin Gao

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Methods Mentioned

BETA
FACS
flow cytometry
PCR
light microscopy
flow

Software Mentioned

NIH ImageJ
Diva
FlowJo
ImageJ

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