Observing Extracellular Vesicles Originating from Endothelial Cells in Vivo Demonstrates Improved Astrocyte Function Following Ischemic Stroke via Aggregation-Induced Emission Luminogens

Extracellular vesicles (EVs) obtained from endothelialcells (ECs)have significant therapeutic potential in the clinical managementof individuals with ischemic stroke (IS) because they effectivelytreat ischemic stroke in animal models. However, because molecularprobes with both high labeling efficiency and tracer stability arelacking, monitoring the actions of EC-EVs in the brain remains difficult.The specific intracellular targets in the brain that EC-EVs act onto produce their protective effects are still unknown, greatly impedingtheir use in clinical settings. For this research, we created a probethat possessed aggregation-induced emission (AIE) traits (namely,TTCP), enabling the effective labeling of EC-EVs while preservingtheir physiological properties. In vitro, TTCP simultaneouslyhad a higher EC-EV labeling efficiency and better tracer stabilitythan the commercial EV tags PKH-67 and DiI. In vivo, TTCP precisely tracked the actions of EC-EVs in a mouse IS modelwithout influencing their protective effects. Furthermore, throughthe utilization of TTCP, it was determined that astrocytes were thespecific cells affected by EC-EVs and that EC-EVs exhibited a safeguardingimpact on astrocytes following cerebral ischemia-reperfusion (I/R)injury. These protective effects encompassed the reduction of theinflammatory reaction and apoptosis as well as the enhancement ofcell proliferation. Further analysis showed that miRNA-155-5p carriedby EC-EVs is responsible for these protective effects via regulationof the c-Fos/AP-1 pathway; this information provided a strategy forIS therapy. In conclusion, TTCP has a high EC-EV labeling efficiencyand favorable in vivo tracer stability during IStherapy. Moreover, EC-EVs are absorbed by astrocytes during cerebralI/R injury and promote the restoration of neurological function throughthe regulation of the c-Fos/AP-1 signaling pathway.