Corin inhibits microglial inflammatory activation by suppressing mitochondrial dysfunction in intracerebral hemorrhage

Microglial activation driving neuroinflammation is a key factor in secondary brain injury after intracerebral hemorrhage (ICH); however, the regulatory mechanisms remain unknown. This study investigates how corin influences microglial inflammatory activation and its underlying mechanisms. Corin expression in rat ICH brain tissue was assessed at multiple time points. To assess corin's effect on neurological function and microglial inflammation, ICH rats and oxygen-glucose deprivation plus hemin (OGD/H)-stimulated HAPI microglia were treated with corin-encoding lentivirus. Neurobehavioral performance was evaluated using the Morris water maze (MWM). Microglial activation was assessed via Iba-1, iNOS, and Arg-1 expression, cytokine secretion, and migration assays. To determine whether AMPK mediates corin's effects, cells were co-treated with Compound C (an AMPK inhibitor) and corin lentivirus. Corin expression decreased in ICH rat brain tissue, reaching its lowest level on day 3 post-ICH. Corin overexpression protected against ICH-induced neuronal apoptosis and improved neurological deficits as confirmed by MWM. Moreover, corin overexpression reduced microglial activation and inflammation in both ICH rats and OGD/H-stimulated microglial cells, ameliorated mitochondrial dysfunction, and increased the p-AMPK/AMPK ratio. The protective effects of corin on cell migration, inflammation, and mitochondrial function were reversed by Compound C, indicating AMPK is a downstream mediator of corin. Targeting corin offers a promising therapeutic strategy for ICH by reducing neuroinflammation and mitochondrial damage through AMPK activation and modulation of microglial inflammatory phenotype polarization. [BMB Reports 2026; 59(2): 143-150].