Student Sun Yat-Sen University Guangzhou, Guangdong, China (People's Republic)
Objectives : Post-stroke exercise has emerged as a promising intervention to enhance neurological recovery, with muscle contractions during physical activity promoting the release of Irisin. Recent research indicates that Irisin may confer neuroprotective benefits by crossing the blood-brain barrier (BBB) and reducing ischemic injury, although the underlying mechanisms remain incompletely understood. This study aims to investigate potential alternative therapeutic strategies for stroke patients with motor function impairments.
Design: Male C57BL/6J mice (8-10 weeks old) underwent 60 minutes of transient middle cerebral artery occlusion (tMCAO) with or without subsequent exercise training. Brain tissue analysis included bulk RNA-seq, flow cytometry, and immunofluorescence staining. Microglia-derived migrasomes post-stroke were characterized using 4D-DIA quantitative proteomics. Bulk RNA-seq was performed on Irisin-treated primary microglia.
Results: Following stroke, microglia in the infarct region produced migrasomes, which were subsequently internalized by damaged neurons. These migrasomes transferred brevican, suppressing neuronal apoptosis. Notably, exercise-induced Irisin from skeletal muscle enhanced migrasome production in microglia via the Integrin αVβ5 /Rac1 signaling pathway, ultimately promoting neuronal survival and supporting neurological recovery after stroke.
Conclusion: Our findings suggest that microglia-derived migrasomes could be a novel therapeutic candidate for improving stroke outcomes, particularly in patients with significant motor deficits.
