Migrasomes in Ischemic Stroke: Molecular Landscape and Pathophysiological Impact.

Ischemic stroke (IS) initiates complex systemic responses that extend beyond focal brain injury. To capture these multifaceted changes, proteomics, untargeted metabolomics, and lipidomics are integrated from IS patients spanning a range of clinical severities. This multi-omics approach reveals distinct molecular subtypes characterized by immune activation, oxidative stress, and metabolic dysregulation. Notably, elevated levels of migrasomes are identified in patient plasma and mouse brain tissue. Proteomic profiling of these migrasomes shows enrichment in complement, coagulation, and cholesterol-associated pathways. Functional assays further demonstrate that migrasomes derived from peripheral immune cells exacerbate ischemic injury and intensify post-stroke inflammation. Together, these findings position migrasomes as critical drivers of IS pathophysiology and highlight them as promising targets for therapeutic intervention.