Ginkgolide B attenuates post-stroke cognitive impairment via exosomal miR-299a-3p regulation of the TRIL/PI3K/AKT...

Post-stroke cognitive impairment (PSCI) is a frequent and disabling outcome of ischemic stroke, yet effective therapeutic options remain limited. In the present study, Ginkgolide B (GB), a major diterpene lactone component of Ginkgo biloba, demonstrated protective effects in both OGD/R-induced microglial injury and MCAO rat models. GB administration was associated with enhanced cell proliferation, reduced apoptosis, decreased ROS production, increased GSH levels, and downregulation of proinflammatory cytokines. Exosomal miRNA sequencing identified miR-299a-3p as a potential regulator, and functional analyses confirmed its role in targeting TRIL and modulating the PI3K/AKT pathway. Both GB treatment and miR-299a-3p overexpression promoted PI3K/AKT phosphorylation, whereas TRIL overexpression partially attenuated these effects. Collectively, these findings suggest that GB may alleviate PSCI through an exosomal miR-299a-3p-TRIL-PI3K/AKT axis, providing experimental evidence that could inform the development of novel therapeutic approaches.