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

  • Int Immunopharmacol. 2019 Oct;75:105771. doi: 10.1016/j.intimp.2019.105771.
Hongsheng Liang  1 ,  Yong Sun  2 ,  Aili Gao  3 ,  Nannan Zhang  4 ,  Ying Jia  5 ,  Shanshan Yang  6 ,  Meng Na  1 ,  Huailei Liu  1 ,  Xingbo Cheng  1 ,  Xiaofeng Fang  1 ,  Wei Ma  1 ,  Xiangtong Zhang  7 ,  Fan Wang  8
Affiliations
  • 1. Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
  • 2. Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China; Department of Neurosurgery, Xinyang Central Hospital, Xinyang, P.R. China.
  • 3. School of Life Science, Northeast Agricultural University, Harbin, P.R. China.
  • 4. Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P.R. China.
  • 5. Department of Pathology, First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
  • 6. Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
  • 7. Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China. Electronic address: [email protected].
  • 8. Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P.R. China. Electronic address: [email protected].
PMID: 31352322 DOI: 10.1016/j.intimp.2019.105771
Abstract

Objective: Intracerebral hemorrhage (ICH) is acknowledged as a serious clinical problem lacking effective treatments. And caspase-1-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-1β/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.

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