Recent studies have reported that receptor-interacting protein kinase 3 (RIPK3)-dependent necroptosis is related to the pathological process of intracerebral hemorrhage (ICH). Some studies support the view that inhibiting necroptosis is a key mechanism preventing inflammation. Inflammation is a crucial factor contributing to neurological injuries and unfavorable outcomes after ICH. The

There exerted an association between RIPK3 and MCP-1. The inhibition of RIPK3 alleviated MCP-1-mediated inflammation following ICH.

An ICH model was established in C57BL/6 mice by injecting collagenase IV into the right basal ganglia. The RIPK3 inhibitor GSK872 was administered through intraventricular injection. Then, we assessed brain edema and neurobehavioral function. Western blotting was employed to detect changes in RIPK3, phospho-mixed lineage kinase domain-like protein (p-MLKL), MCP-1, phospho-c-Jun N-terminal kinase (p-JNK) and interleukin 6 (IL-6) levels in the brain tissue. The localization of RIPK3 and MCP-1 was observed using immunofluorescence staining. Co-immunoprecipitation was performed to determine the interaction between RIPK3 and MCP-1.

Compared with the sham group, the levels of RIPK3, p-MLKL, MCP-1, p-JNK and IL-6 were increased post-ICH. GSK872 pretreatment significantly reduced RIPK3, p-MLKL, MCP-1, p-JNK and IL-6 expression, accompanied by mitigated cerebral edema and neurobehavioral defects. RIPK3 and MCP-1 colocalized in the perinuclear region after ICH. We detected the formation of the RIPK3-MCP-1 complex in ICH brain tissue. Conclusions: There exerted an association between RIPK3 and MCP-1. The inhibition of RIPK3 alleviated MCP-1-mediated inflammation following ICH.