Journal
CHINESE JOURNAL OF TRAUMATOLOGY
Volume 18, Issue 5, Pages 254-258Publisher
ELSEVIER INC
DOI: 10.1016/j.cjtee.2015.11.010
Keywords
Hemin; Microglia; NLRP3 protein; N-methyl-D-aspartic acid receptor 1; Inflammasome
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Funding
- Special Fund for Major State Basic Research Project of China (973 projects) [2014CB541605]
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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-1 beta 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-1 beta 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-1 beta 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. (C) 2015 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V.
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