Recent advances in research on novel therapeutic mechanisms and strategies for exosome-based treatment of ischemic stroke

Abstract

Ischemic stroke (IS) accounts for over 80% of all stroke cases, featuring high disability, mortality, and recurrence rates. Conventional intravenous thrombolysis and mechanical thrombectomy are limited by narrow therapeutic windows, reperfusion injury, and the blood–brain barrier (BBB), which impedes the entry of neuroprotective agents into the brain parenchyma. Exosomes (Exos) are cell-secreted nanoscale extracellular vesicles (EVs) that carry miRNAs, proteins, and lipids, with low immunogenicity, BBB permeability, and ease of genetic modification, making them promising cell-free therapeutic agents for central nervous system (CNS) disorders. Exos alleviate cerebral ischemia-reperfusion injury by suppressing multiple forms of programmed cell death, oxidative stress, and neuroinflammation, repairing the BBB, and facilitating angiogenesis and neurogenesis. Genetic engineering, surface peptide modification, and drug loading further enhance brain-targeted exosomal enrichment. This review systematically summarises Exos biogenesis, multi-pathway neural repair mechanisms mediated by exosomal miRNAs, engineered delivery strategies, translational bottlenecks, and future research directions, aiming to provide theoretical support for the clinical transformation of Exos therapy for IS.