Therapeutic Potential of Astrocyte-Derived Extracellular Vesicles in Post-Stroke Recovery: Behavioral and MRI-Based Insights from a Rat Model

Astrocyte-derived extracellular vesicles (ADEVs) have emerged as promising neuroprotective agents for ischemic stroke. In this study, we evaluated the therapeutic potential of hypoxia-conditioned ADEVs (HxEVs) administered intracerebroventricularly in a rat model of transient middle cerebral artery occlusion (tMCAO). Serial magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was performed at 1, 7, 14, and 21 days post-stroke. HxEV treatment produced a significant reduction in infarct volume from day 1, sustained through day 21, and was accompanied by improvements in motor and sensory recovery. DTI analyses showed progressive normalization of fractional anisotropy (FA) and radial diffusivity (RD), particularly in the corpus callosum and striatum, reflecting microstructural repair. In contrast, mean diffusivity (MD) was less sensitive to these treatment effects. Regional differences in therapeutic response were evident, with earlier and more sustained recovery in the corpus callosum than in other brain regions. Histological findings confirmed greater preservation of dendrites and axons in HxEV-treated animals, supporting the role of these vesicles in accelerating post-stroke neurorepair. Together, these results demonstrate that hypoxia-conditioned ADEVs promote both structural and functional recovery after ischemic stroke. They also highlight the value of DTI-derived biomarkers as non-invasive tools to monitor neurorepair. The identification of region-specific therapeutic effects and the validation of reliable imaging markers provide a strong foundation for future research and development.