Hypoxia-Induced Neural-BBB Coupling via Extracellular Vesicles Delivering CircOGDH

CircOGDH is a circular RNA linked to hypoxic neurons. In this study, we investigated how neuron-derived CircOGDH affects BBB-associated endothelial cells under hypoxic conditions.

We reduced neuronal CircOGDH expression in MCAO/R(middle cerebral artery occlusion/reperfusion) mice using a neuron-specific AAV, which led to compromised BBB structure and maintenance in ischemic stroke mice. We found that giving CircOGDH-rich sEVs(small extracellular vesicles) to brain tumors helped blood vessels stay integrity in a glioblastoma model. In addition, we revealed that hypoxic neurons transfer CircOGDH from sEVs to ECs in vitro co-culture system, leading to increased COL4A4 expression and improved ECs functionality.