CCR2 deficiency in monocytes impairs angiogenesis and functional recovery after ischemic stroke in mice.
J Cereb Blood Flow Metab
; 40(1_suppl): S98-S116, 2020 12.
Article
in En
| MEDLINE
| ID: mdl-32151226
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 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Monocytes
/
Receptors, CCR2
/
Ischemic Stroke
Limits:
Animals
Language:
En
Journal:
J Cereb Blood Flow Metab
Year:
2020
Document type:
Article
Affiliation country:
España