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
CNS Neuroscience & Therapeutics, 2026
Huang R., Gao L., Dai Y., Li S., Guru J., Li M., Chen Y., Wu B., Ru X., Gong Q., Tang J., Zhu G., Chen Y.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurovascular Diseases Environmental Health & Toxicology | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
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.