Wnt-3a alleviates neuroinflammation after ischemic stroke by modulating the responses of microglia/macrophages and astrocytes
| Autor: | Linghui Liao, Ruiming Guo, Yongxin Zhang, Di Zhang, Qianqian Xiao, Hong Lu, Xiaojie Fu, Zhengfang Lu, Jiang Man, Xianliang Liu, Jianping Wang, Yufeng Gao, Zhen Zhang, Lie Yu, Kefei Cui |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Immunology Inflammation Pharmacology 03 medical and health sciences 0302 clinical medicine Wnt3A Protein medicine Animals Immunologic Factors Immunology and Allergy Administration Intranasal Neuroinflammation Glial fibrillary acidic protein biology Microglia business.industry Macrophages Wnt signaling pathway Infarction Middle Cerebral Artery Mice Inbred C57BL Stroke Neuroprotective Agents 030104 developmental biology medicine.anatomical_structure Interleukin 15 Astrocytes 030220 oncology & carcinogenesis biology.protein Tumor necrosis factor alpha medicine.symptom business Astrocyte |
| Zdroj: | International Immunopharmacology. 75:105760 |
| ISSN: | 1567-5769 |
| Popis: | Neuroinflammation crucially influences functional recovery after ischemic stroke. Wnt-3a, a novel Wnt protein that specifically promotes Wnt/β-catenin signaling pathway, has been shown to regulate apoptosis and cell proliferation, but how it affects ischemic stroke-induced toxic brain inflammation remains unknown. Using a transient middle cerebral artery occlusion (tMCAO) mouse model in this study, we found that intranasal Wnt-3a-treated tMCAO mice had apparently reduced infarct volume and decreased brain water content after being allowed to recover for 72 h, as well as better neurologic outcomes on days 3, 7, and 14. Mice received Wnt-3a had significantly fewer tMCAO-induced peri-infarct TUNEL-positive cells compared with those received vehicle. Further, Wnt-3a-delivered tMCAO mice had notably fewer peri-infarct CD68-positive cells and lower ionized calcium-binding adapter molecule (Iba)-1 protein level. Wnt-3a significantly downregulated the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α, and upregulated the expression of arginase 1 (Arg1) and CD206. Finally, Wnt-3a obviously decreased the number of tMCAO-induced peri-infarct glial fibrillary acidic protein (GFAP)/C3-positive cells, increased the number of GFAP/S100A10-positive cells, attenuated the protein levels of GFAP and interleukin 15 (IL15), and elevated IL33 protein level. Our findings suggest that intranasal Wnt-3a could ameliorate toxic responses of microglia/macrophages and astrocytes in ischemic brain injury, supporting that Wnt-3a might be potentially appropriate for ischemic stroke treatment functioning as an immunomodulatory agent. |
| Databáze: | OpenAIRE |
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