Academic Journal
Microglia exacerbate white matter injury via complement C3/C3aR pathway after hypoperfusion
| العنوان: | Microglia exacerbate white matter injury via complement C3/C3aR pathway after hypoperfusion |
|---|---|
| المؤلفون: | Zhang, Lin-Yuan, Pan, Jiaji, Mamtilahun, Muyassar, Zhu, Yuan, Wang, Liping, Venkatesh, Ashwin, Shi, Rubing, Tu, Xuanqiang, Jin, Kunlin, Wang, Yongting, Zhang, Zhijun, Yang, Guo-Yuan |
| المصدر: | Theranostics |
| بيانات النشر: | Ivyspring International Publisher |
| سنة النشر: | 2022 |
| المجموعة: | UNTHSC Scholarly Repository (University. of North Texas Health Science Center) |
| مصطلحات موضوعية: | chronic cerebral hypoperfusion, complement, inflammation, microglia, white matter injury, Animals, Brain Injuries / metabolism, Brain Injuries / pathology, Brain Ischemia / metabolism, Brain Ischemia / pathology, Complement C3 / metabolism, Complement Pathway, Classical, Inflammation / metabolism, Inflammation / pathology, Male, Mice, Inbred C57BL, Knockout, Microglia / pathology, Perfusion, Rats, Sprague-Dawley, Receptors, G-Protein-Coupled / metabolism, White Matter / metabolism, White Matter / pathology |
| الوصف: | Microglial activation participates in white matter injury after cerebral hypoperfusion. However, the underlying mechanism is unclear. Here, we explore whether activated microglia aggravate white matter injury via complement C3-C3aR pathway after chronic cerebral hypoperfusion. Methods: Adult male Sprague-Dawley rats (n = 80) underwent bilateral common carotid artery occlusion for 7, 14, and 28 days. Cerebral vessel density and blood flow were examined by synchrotron radiation angiography and three-dimensional arterial spin labeling. Neurobehavioral assessments, CLARITY imaging, and immunohistochemistry were performed to evaluate activation of microglia and C3-C3aR pathway. Furthermore, C3aR knockout mice were used to establish the causal relationship of C3-C3aR signaling on microglia activation and white matter injury after hypoperfusion. Results: Cerebral vessel density and blood flow were reduced after hypoperfusion (p<0.05). Spatial learning and memory deficits and white matter injury were shown (p<0.05). These impairments were correlated with aberrant microglia activation and an increase in the number of reactive microglia adhering to and phagocytosed myelin in the hypoperfusion group (p<0.05), which were accompanied by the up-regulation of complement C3 and its receptors C3aR (p<0.05). Genetic deletion of C3ar1 significantly inhibited aberrant microglial activation and reversed white matter injury after hypoperfusion (p<0.05). Furthermore, the C3aR antagonist SB290157 decreased the number of microglia adhering to myelin (p<0.05), attenuated white matter injury and cognitive deficits in chronic hypoperfusion rats (p<0.05). Conclusions: Our results demonstrated that aberrant activated microglia aggravate white matter injury via C3-C3aR pathway during chronic hypoperfusion. These findings indicate C3aR plays a critical role in mediating neuroinflammation and white matter injury through aberrant microglia activation, which provides a novel therapeutic target for the small vessel disease and ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| تدمد: | 1838-7640 |
| Relation: | https://doi.org/10.7150/thno.35841; Zhang, L. Y., Pan, J., Mamtilahun, M., Zhu, Y., Wang, L., Venkatesh, A., Shi, R., Tu, X., Jin, K., Wang, Y., Zhang, Z., & Yang, G. Y. (2020). Microglia exacerbate white matter injury via complement C3/C3aR pathway after hypoperfusion. Theranostics, 10(1), 74-90. https://doi.org/10.7150/thno.35841; https://hdl.handle.net/20.500.12503/31704; 10 |
| الاتاحة: | https://hdl.handle.net/20.500.12503/31704 |
| Rights: | Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0/ ; © The author(s). |
| رقم الانضمام: | edsbas.397377AA |
| قاعدة البيانات: | BASE |
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