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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 1).

The caspase 1 T activation complexes (inflammasomes) can facilitate caspase-1 and IL-1β processing, which amplifies the inflammatory response.

In a study Li et al. examined whether caspase-1 activation contributes to irradiation-induced damage to neural stem and progenitor cells (NSPCs). They found that X-ray irradiation induced activation of caspase-1 in NSPCs in vitro and in vivo. Next, using a caspase-1 inhibitor (Ac-YVAD-CMK) to block caspase-1 activation in vitro and in vivo, we further demonstrated that X-ray irradiation may inhibit proliferation, induce senescence of NSPCs through caspase-1 activation. Together, these results suggest that caspase-1 activation is involved in irradiation-induced damage to NSPCs 2)

Liang H, Sun Y, Gao A, Zhang N, Jia Y, Yang S, Na M, Liu H, Cheng X, Fang X, Ma W, Zhang X, Wang F. Ac-YVAD-cmk improves neurological function by inhibiting caspase-1-mediated inflammatory response in the intracerebral hemorrhage of rats. Int Immunopharmacol. 2019 Jul 25;75:105771. doi: 10.1016/j.intimp.2019.105771. [Epub ahead of print] PubMed PMID: 31352322.
Li T, Li L, Li F, Liu Y. X-ray irradiation accelerates senescence in hippocampal neural stem/progenitor cells via caspase-1 activation. Neurosci Lett. 2015 Jan 12;585:60-5. doi: 10.1016/j.neulet.2014.11.028. Epub 2014 Nov 20. PubMed PMID: 25445379.
ac-yvad-cmk.txt · Last modified: 2019/07/31 11:45 by administrador