Proteomic characterization of astrocyte-derived extracellular vesicles under hypoxia

This study investigated the role of astrocyte-derived EVs in neuroprotection and tissue recovery post-ischemia. Cortical astrocytes were cultured under normoxic and hypoxic conditions to harvest extracellular vesicles (EVs). The EVs were then administered to rats that had undergone experimental stroke. We assessed infarct volume, neuronal survival, and neurological function, and utilized label-free mass spectrometry-based proteomics to evaluate the hypoxia-induced changes in the EV proteome. Administration of astrocyte-derived EVs significantly reduced infarct volume, improved neurological function, and mitigated blood-brain barrier (BBB) permeability. Proteomic analysis revealed a differential expression of 67 upregulated proteins under hypoxic conditions and 37 downregulated proteins under normoxic conditions, highlighting the protective protein signatures elicited by astrocytes. Our findings underscore the role of astrocyte-derived EVs in fostering a conducive environment for neuronal survival under hypoxic stress. (Supported by DGAPA-PAPIIT IN207020 and IN214723 and CONACYT A1-S-13219).