Mast Cells Mediate Inflammatory Injury and Aggravate Neurological Impairment in Experimental Subarachnoid Hemorrhage Through Microglial PAR-2 Pathway
| Autor: | Hangzhe Xu, Huaijun Chen, Chen Zhong, Bing Qin, Hanhai Zeng, Lin Wang, Yucong Peng, Chaoran Xu, Guangyu Ying, Yong Cai, Gao Chen, C. Charles Gu, Shengjun Zhou, Jianfeng Zhuang, Jianru Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Subarachnoid hemorrhage
subarachnoid hemorrhage Perforation (oil well) microglia mast cells PAR-2 Neurosciences. Biological psychiatry. Neuropsychiatry Context (language use) Tryptase Pharmacology neuroinflammation Cellular and Molecular Neuroscience medicine cardiovascular diseases Neuroinflammation Original Research Microglia biology business.industry Degranulation medicine.disease humanities Pathophysiology nervous system diseases medicine.anatomical_structure biology.protein business Neuroscience RC321-571 |
| Zdroj: | Frontiers in Cellular Neuroscience, Vol 15 (2021) Frontiers in Cellular Neuroscience |
| ISSN: | 1662-5102 |
| DOI: | 10.3389/fncel.2021.710481 |
| Popis: | Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease with high mortality and disability. Aberrant neuroinflammation has been identified as a critical factor accounting for the poor prognosis of SAH patients. Mast cells (MCs), the sentinel cells of the immune system, play a critical in the early immune reactions and participate in multiple pathophysiological process. However, the exact role of MCs on the pathophysiological process after SAH has not been fully understood. The current study was conducted to determine the role of MCs and MC stabilization in the context of SAH. Mouse SAH model was established by endovascular perforation process. Mice received saline or cromolyn (MC stabilizer) or compound 48/80 (MCs degranulator). Post-SAH evaluation included neurobehavioral test, western blot, immunofluorescence, and toluidine blue staining. We demonstrated that SAH induced MCs activation/degranulation. Administration of MC stabilizer cromolyn conferred a better neurologic outcome and decreased brain edema when compared with SAH+vehicle group. Furthermore, cromolyn significantly inhibited neuroinflammatory response and alleviated neuronal damage after SAH. However, pharmacological activation of MCs with compound 48/80 dramatically aggravated SAH-induced brain injury and exacerbated neurologic outcomes. Notably, pharmacological inhibition of microglial PAR-2 significantly reversed MCs-induced inflammatory response and neurological impairment. Additionally, the effect of MCs-derived tryptase in mediating neuroinflammation was also abolished by the microglial PAR-2 blockage in vitro. Taken together, MCs yielded inflammatory injury through activating microglia-related neuroinflammation after SAH. These data shed light on the notion that MCs might be a novel and promising therapeutic target for SAH. |
| Databáze: | OpenAIRE |
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