Olink Proteomics Reveals <scp>CCL2</scp> Aggravates Perihematomal Edema After Intracerebral Hemorrhage in High‐Altitude Migrants Via <scp>CCR2</scp> / <scp>NF</scp> ‐ <scp>κB</scp> ‐Mediated Blood–Brain Barrier Disruption

AIMS: To identify key environment-sensitive inflammatory factors and clarify their pathogenic mechanisms in severe secondary brain injury after intracerebral hemorrhage (ICH) in high-altitude migrants-addressing the critical gap that elevated hemoglobin alone cannot fully explain the underlying pathogenesis and investigating chronic inflammation as a key pathogenic driver. METHODS: Olink proteomics profiling was performed in 66 high-altitude migrants and 22 plain-resident controls to identify differentially expressed inflammatory factors. Rat high-altitude ICH models were subsequently established and treated with AAV-CCL2, a CCL2-neutralizing antibody, recombinant CCL2, and a CCR2 inhibitor, and the results were validated through transcriptomic and multidimensional methods. RESULTS: CCL2 was the most significantly upregulated environmentally sensitive inflammatory factor and was weakly correlated with hemoglobin levels. High-altitude rats had higher levels of post-ICH CCL2, which was associated with severe blood-brain barrier (BBB) disruption; CCR2 blockade abolished CCL2-induced BBB damage and neuroinflammation. CONCLUSIONS: CCL2 plays an important role in secondary injury after high-altitude ICH, mainly by amplifying inflammation and exacerbating damage via the CCL2-CCR2-NF-κB pathway and may serve as a potential therapeutic target.