Universität zu Köln

Pedragosa, Jordi, Miro-Mur, Francesc, Otxoa-de-Amezaga, Amaia, Justicia, Carles, Ruiz-Jaen, Francisca, Ponsaerts, Peter ORCID: 0000-0002-1892-6499, Pasparakis, Manolis ORCID: 0000-0002-9870-0966 and Planas, Anna M. (2020). CCR2 deficiency in monocytes impairs angiogenesis and functional recovery after ischemic stroke in mice. J. Cereb. Blood Flow Metab., 40 (1_SUPPL). S. S98 - 19. THOUSAND OAKS: SAGE PUBLICATIONS INC. ISSN 1559-7016

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pedragosa, Jordi UNSPECIFIED UNSPECIFIED UNSPECIFIED Miro-Mur, Francesc UNSPECIFIED UNSPECIFIED UNSPECIFIED Otxoa-de-Amezaga, Amaia UNSPECIFIED UNSPECIFIED UNSPECIFIED Justicia, Carles UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruiz-Jaen, Francisca UNSPECIFIED UNSPECIFIED UNSPECIFIED Ponsaerts, Peter UNSPECIFIED orcid.org/0000-0002-1892-6499 UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED Planas, Anna M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-341304
DOI:	10.1177/0271678X20909055
Journal or Publication Title:	J. Cereb. Blood Flow Metab.
Volume:	40
Number:	1_SUPPL
Page Range:	S. S98 - 19
Date:	2020
Publisher:	SAGE PUBLICATIONS INC
Place of Publication:	THOUSAND OAKS
ISSN:	1559-7016
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHEMOATTRACTANT PROTEIN-1; MACROPHAGE PLASTICITY; TISSUE-REPAIR; INJURY; CELLS; POLARIZATION; DIFFERENTIATION; QUANTIFICATION; INFLAMMATION; MECHANISMS Multiple languages Endocrinology & Metabolism; Hematology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/34130