CCR2 deficiency in monocytes impairs angiogenesis and functional recovery after ischemic stroke in mice.

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Jordi PedragosaAnna M Planas

Abstract

Inflammatory Ly6ChiCCR2+ monocytes infiltrate the brain after stroke but their functions are not entirely clear. We report that CCR2+ monocytes and CCR2+ lymphocytes infiltrate the brain after permanent ischemia. To underscore the role of CCR2+ monocytes, we generated mice with selective CCR2 deletion in monocytes. One day post-ischemia, these mice showed less infiltrating monocytes and reduced expression of pro-inflammatory cytokines, markers of alternatively macrophage activation, and angiogenesis. Accordingly, Ly6Chi monocytes sorted from the brain of wild type mice 24 h post-ischemia expressed pro-inflammatory genes, M2 genes, and pro-angiogenic genes. Flow cytometry showed heterogeneous phenotypes within the infiltrating Ly6ChiCCR2+ monocytes, including a subgroup of Arginase-1+ cells. Mice with CCR2-deficient monocytes displayed a delayed inflammatory rebound 15 days post-ischemia that was not found in wild type mice. Furthermore, they showed reduced angiogenesis and worse behavioral performance. Administration of CCR2+/+ bone-marrow monocytes to mice with CCR2-deficient monocytes did not improve the behavioral performance suggesting that immature bone-marrow monocytes lack pro-reparative functions. The results show that ...Continue Reading

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Citations

Oct 4, 2020·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Dong HanYan Gao
Nov 17, 2020·Frontiers in Neurology·Joohyun ParkJong Eun Lee
Oct 16, 2020·Brain Pathology·Daniel BerchtoldAndreas Meisel
Mar 3, 2021·CNS Neuroscience & Therapeutics·Junxuan LyuXiaoyan Jiang
Apr 6, 2021·Molecular Neurobiology·Kanika VasudevaAnjana Munshi
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Jun 27, 2021·Pharmacology & Therapeutics·V Durán-LaforetI Lizasoain
Jun 27, 2021·Molecular Neurodegeneration·Hila Ben-YehudaMichal Schwartz

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Methods Mentioned

BETA
flow cytometry
FACS
Fluorescence Activated Cell Sorting
PCR
flow
confocal microscopy

Software Mentioned

FlowJo
iCycler iQTM Real - time Detection System
GraphPad Prism
FacsDiva
ImageJ
Primer
GraphPad Quickcalcs
Adobe Photoshop
LAS
power

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