CCR2 deficiency in monocytes impairs angiogenesis and functional recovery after ischemic stroke in mice
| العنوان: | CCR2 deficiency in monocytes impairs angiogenesis and functional recovery after ischemic stroke in mice |
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| المؤلفون: | Jordi Pedragosa, Peter Ponsaerts, Carles Justicia, Francesc Miró-Mur, Francisca Ruiz-Jaén, Manolis Pasparakis, Anna M. Planas, Amaia Otxoa-de-Amezaga |
| المصدر: | J Cereb Blood Flow Metab Journal of cerebral blood flow and metabolism Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | SAGE Publications, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, CCR2, Pathology, medicine.medical_specialty, Angiogenesis, Receptors, CCR2, animal diseases, Permanent middle cerebral artery occlusion, Neovascularization, Physiologic, Inflammation, Monocytes, 03 medical and health sciences, Mice, 0302 clinical medicine, parasitic diseases, medicine, Animals, Stroke, 030304 developmental biology, Ischemic Stroke, 0303 health sciences, business.industry, Macrophages, Brain, hemic and immune systems, Original Articles, medicine.disease, Functional recovery, Disease Models, Animal, Neurology, Ischemic stroke, Human medicine, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, Repair, 030217 neurology & neurosurgery |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 0271-678X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4f64d30d94dd8430097c5a34785fd7eTest https://europepmc.org/articles/PMC7687030Test/ |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a4f64d30d94dd8430097c5a34785fd7e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 0271678X |
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