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

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.