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

Inflammatory Ly6C(hi)CCR2(+) 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, Ly6C(hi) 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 Ly6C(hi)CCR2(+) 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 CCR2(+) monocytes contribute to acute post-ischemic inflammation and participate in functional recovery. The study unravels heterogeneity in the population of CCR2(+) monocytes infiltrating the ischemic brain and suggests that pro-reparative monocyte subsets promote functional recovery after ischemic stroke.

Publication year:2020

Keywords:A1 Journal article

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BOF-publication weight:3

CSS-citation score:3

Authors:International

Authors from:Higher Education

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