Academic Journal
Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain
| العنوان: | Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain |
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| المؤلفون: | Zhang, Wenting, Zhao, Jingyan, Wang, Rongrong, Jiang, Ming, Ye, Qing, Smith, Amanda D., Chen, Jun, Shi, Yejie |
| المساهمون: | American Heart Association, Medical Center, University of Pittsburgh, U.S. Department of Veterans Affairs |
| المصدر: | CNS Neuroscience & Therapeutics ; volume 25, issue 12, page 1329-1342 ; ISSN 1755-5930 1755-5949 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2019 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Aims Blood‐borne monocytes/macrophages infiltrate the brain in massive numbers after ischemic stroke, but their impact on poststroke brain injury and recovery remains elusive. This study examined the transcriptomic changes in monocytes/macrophages after ischemic stroke and the functional implications of these changes, particularly with regards to the contribution of these cells to the phagocytic clearance of dead/dying cells (efferocytosis) in the poststroke brain. Methods We performed whole‐genome RNA sequencing on the monocyte/macrophage population sorted from mouse brain and peripheral blood 5 days after permanent focal cerebral ischemia. In addition, the spatial and temporal profiles of macrophage efferocytosis were examined in vivo by immunohistochemistry 3‐7 days after brain ischemia. Results Robust transcriptomic changes occurred in monocytes/macrophages upon infiltrating the poststroke brain. Functional enrichment analysis revealed a transcriptome of brain macrophages that strongly favored efferocytic activity. A large number of efferocytosis‐related genes were upregulated in brain macrophages, the products of which are essential components involved in various steps of efferocytosis, such as chemotaxis, recognition of dead cells, engulfment, and processing of phagosomes. The efferocytic activity of brain macrophages were verified by immunohistochemistry, wherein Iba1‐labeled microglia/macrophages effectively cleared apoptotic neurons in the infarct during the subacute stage after brain ischemia. We also identified PPARγ and STAT6 as potential upstream regulators that shaped this proefferocytic and inflammation‐resolving transcriptome of macrophages in the poststroke brain. Conclusion Macrophages play a crucial role in the phagocytic clearance of dead neurons after ischemic stroke and promote the resolution of inflammation in the brain. Molecular therapies that enhance macrophage efferocytic capability may be promising treatments for ischemic stroke by facilitating inflammation resolution, brain ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/cns.13256 |
| الاتاحة: | https://doi.org/10.1111/cns.13256 https://onlinelibrary.wiley.com/doi/pdf/10.1111/cns.13256 https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cns.13256 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.C8845FDE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/cns.13256 |
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