Exosomes Released by Cerebrolysin-Treated Cerebral Endothelial Cells Reverse Fibrin- or tPA-Impaired Endothelial Cell Permeability

Cerebrolysin has a salutary effect on impaired cerebral endothelial cell (CEC) permeability. Using an in vitro endothelial permeability assay, the present study tested the hypothesis that exosomes released by Cerebrolysin-treated CECs (Cerebro-Exos) have a robust therapeutic effect on dysfunctional CECs. Stoichiometric analysis showed marked differences in cargo profiles between Cerebro-Exos and exosomes derived from CECs without Cerebrolysin treatment (Naïve-Exos), in which Cerebro-Exos were highly enriched with metabolic and tight junction related proteins compared to Naïve-Exos. Cerebro-Exos had a superior effect compared to Naïve-Exos on restoring CEC integrity impaired by fibrin and tissue plasminogen activator (tPA). Treatment of fibrin- and tPA-challenged CECs with Cerebro-Exos robustly reduced fibrin- and tPA-augmented proteins involved in inflammation and coagulation and substantially increased fibrin- and tPA-decreased proteins that are related to tight junctions and metabolism. Collectively, these data indicate that Cerebro-Exos have a broad effect on improvement of dysfunctional CECs, which is likely achieved by the alteration of CEC proteins.