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| Xun Weng,Yan Tan,Xiang Chu,Xiao-Feng Wu,Rui Liu,Yue Tian,Lin Li,Feng Guo,Qing Ouyang,Lei Li.[J].Chin J Traumatol,2015,18(5):254-258. [doi] |
| N-methyl-D-aspartic acid receptor 1 (NMDAR1) aggravates secondary inflammatory damage induced by hemin-NLRP3 pathway after intracerebral hemorrhage |
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| DOI： |
| KeyWord: Hemin
Microglia
NLRP3 protein
N-methyl-D-aspartic acid receptor 1
Inflammasome |
| FundProject: |
| Author Name | Affiliation | | Xun Weng | State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery/Daping Hospital, Third Military Medical University | | Yan Tan | State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery/Daping Hospital, Third Military Medical University | | Xiang Chu | State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery/Daping Hospital, Third Military Medical University | | Xiao-Feng Wu | State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery/Daping Hospital, Third Military Medical University | | Rui Liu | State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery/Daping Hospital, Third Military Medical University | | Yue Tian | State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery/Daping Hospital, Third Military Medical University | | Lin Li | State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery/Daping Hospital, Third Military Medical University | | Feng Guo | State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery/Daping Hospital, Third Military Medical University | | Qing Ouyang | State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery/Daping Hospital, Third Military Medical University | | Lei Li | State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery/Daping Hospital, Third Military Medical University |
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| Abstract: |
| Objective: Inflammation plays a critical role in secondary brain damage after intracerebral hemorrhage (ICH). However, the mechanisms of inflammatory injury following ICH are still unclear, particularly the involvement of NLRP3 inflammasome, which are crucial to sterile inflammatory responses. In this study, we aim to test the hypothesis that NLRP3 signaling pathway takes a vital position in ICH-induced secondary inflammatory damage and detect the role of N-methyl-D-aspartic acid receptor 1 (NMDAR1) in this progress.
Methods: ICH was induced in mice by microinjection of hemin into the striatum. The protein levels of
NMDAR1, NMDAR1 phosphorylation, NLRP3 and IL-1b were measured by Western blot. The binding of
NMDAR1 to NLRP3 was detected by immunoprecipitation.
Results: The expression of NMDAR1, NMDAR1 phosphorylation, NLRP3 and IL-1b were rapidly increased
after ICH. Hemin treatment enhanced NMDAR1 expression and NMDAR1 phosphorylation, as well in
cultured microglial cells treated by hemin. Hemin up-regulated NLRP3 and IL-1b level, which was
reversed by MK801 (NMDAR antagonist) in vitro. Hemin also promoted the binding of NMDAR1 to
NLRP3.
Conclusion: Our findings suggest that NMDAR1 plays a pivotal role in hemin-induced NLRP3-mediated
inflammatory damage through synergistic activation. |
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