# Migrasomes in Ischemic Stroke: Molecular Landscape and Pathophysiological Impact

## TL;DR

This study explores migrasomes in ischemic stroke, revealing their role in immune activation and inflammation, and suggests they could be a new therapeutic target.

## Contribution

The study identifies migrasomes as novel contributors to ischemic stroke pathophysiology through multi-omics and functional assays.

## Key findings

- Migrasomes are elevated in plasma and brain tissue of ischemic stroke patients and mice.
- Migrasomes are enriched in complement, coagulation, and cholesterol-related pathways.
- Immune-cell-derived migrasomes worsen ischemic injury and inflammation in experimental models.

## Abstract

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.

Multi‐omics profiling of stroke patients exposes systemic molecular fingerprints of immune activation, oxidative stress and metabolic collapse. Complement and coagulation cascade, and cholesterol metabolism emerge as shared functional hallmarks of plasma migrasomes in stroke patients and migrasomes isolated from experimental stroke mice. Functional evidence shows these immune‐cell‐derived migrasomes amplify ischemic injury and inflammation, unveiling an unexpected therapeutic node.