4.7 Article

Ac-YVAD-cmk improves neurological function by inhibiting caspase-1-mediated inflammatory response in the intracerebral hemorrhage of rats

期刊

INTERNATIONAL IMMUNOPHARMACOLOGY
卷 75, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.intimp.2019.105771

关键词

Intracerebral hemorrhage; Caspase-1; Ac-YVAD-cmk; Microglia

资金

  1. National Natural Science Foundation of China [81571108, 81201723, 81501050]
  2. Natural Science Foundation of Heilongjiang Province [QC2014C104]
  3. Liande Wu Doctor Funds of Harbin Medical University [WLD-QN1113]
  4. Science and Technology Innovational Foundation of Harbin City [2017RAXXJ042]
  5. Young Talents Project of Northeast Agricultural University [14QC05]

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Objective: Intracerebral hemorrhage (ICH) is acknowledged as a serious clinical problem lacking effective treatments. And caspase-l-mediated inflammatory response happened during the progression of ICH. Therefore, we aimed to investigate the effects of caspase-1 inhibitor Ac-YVAD-cmk on ICH. Materials and methods: Microglia cells were isolated and activated by thrombin for 24 h. Then the transcript and protein expressions of NLRP3 and inflammatory factors were assessed by RT-PCR and western blotting. Moreover, Ac-YVAD-cmk was injected into the ICH model. The mNSS and brain water content were tested at 24 h post-ICH. Finally, the pathological changes of microglia activation following ICH were discovered by the immunohistochemical and HE staining ways. Results: Ac-YVAD-cmk inhibited the activation of pro-caspase-1 and decreased brain edema, in association with decreasing activated microglia and the expression of inflammation-related factors at 24 h post-ICH. Consequently, Ac-YVAD-cmk reduced the release of mature IL-1 beta/IL-18 in perihematoma, improved the behavioral performance, and alleviated microglia in perihematoma region in ICH rats. Conclusions: These results indicate that caspase-1 could amplify the plural inflammatory responses in the ICH. Administration of Ac-YVAD-cmk has the potential to be a novel therapeutic strategy for ICH.

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