Protective Effects of Neuron-Derived Quiescin Sulfhydryl Oxidase 1 Protein on Intracerebral Hemorrhage

Intracranial hemorrhage (ICH) poses a serious risk to human health. The shift between pro-inflammatory (M1) and anti-inflammatory (M2) microglial phenotypes is a complex dynamic process. Quiescin sulfhydryl oxidase 1 (QSOX-1) plays a role in protecting cells from damage caused by oxidative stress and in cellular remodeling processes. This study explored how neuron-derived QSOX-1 protein influences the shift in microglial polarization between the M1 and M2 states, and its subsequent impact on nerve function after ICH.

QSOX-1 expression in the ICH mouse model was detected. Neuroinflammation, nerve damage, microglial phenotype, nerve function changes, and related signaling pathways were observed in mouse or cell models treated with QSOX-1.

After ICH, mass spectrometry analysis identified 353 differential proteins, of which the key role of QSOX-1 was verified by bioinformatics analysis. QSOX-1 in the ICH model was highly expressed in the neurons. After treatment with recombinant QSOX-1, the ICH model exhibited reduced neuroinflammation and nerve damage, improved nerve function, and a shift in microglia towards predominantly anti-inflammatory (M2) phenotypes. In vitro, QSOX-1 intervention led to reduced inflammation and neuronal cell death. When QSOX-1 expression was upregulated in microglia, the cells primarily shifted towards the M2 phenotype. This shift was accompanied by reduced levels of phosphorylated nuclear factor kappa B (NF-kB) and thioredoxin (TRX)-interacting protein (TXNIP)/NLR family pyrin domain containing 3 (NLRP3) protein, along with increased levels of phosphorylated inhibitor of NF-kB alpha (IkB-α) and TRX.

Neuron-derived QSOX-1 protein reduces neuroinflammation and promotes nerve function recovery after ICH by regulating microglia phenotype changes, which may be related to the IkB-α/NF-kB and TRX/TXNIP/NLRP3 axis.