Oxytocin supports the barrier integrity of brain endothelial cells via oxytocin receptors.

Oxytocin plays an emerging role in vascular regulation and neuroprotection, but its effect on brain endothelial cells and blood-brain barrier functionality is not fully defined. To assess oxytocin and vasopressin receptor expression in brain endothelial cells and to evaluate the impact of oxytocin on endothelial barrier integrity under physiological (normoxic) and low-oxygen (hypoxic) conditions we used bEnd.3 brain endothelial cells. Receptor expression was evaluated by real-time PCR and RNAscope. Oxytocin treatment was applied under normoxic and hypoxic conditions and Transendothelial Electrical Resistance and tight junction proteins expression (claudin-5, zonula occludens-1) were analyzed. Our results indicate that 1) bEnd.3 cells express oxytocin and V1a receptors. 2) Activation of the oxytocin receptor enhanced brain endothelial barrier integrity by increasing claudin-5 expression and its localization at the cell surface, without affecting zonula occludens-1.3) Under hypoxic conditions, oxytocin preserved Transendothelial Electrical Resistance and claudin-5 expression at the cell membrane, thereby preventing endothelial barrier impairment. Our findings demonstrate that oxytocin receptor signaling enhances and preserves brain endothelial barrier function, underscoring the relevance of oxytocin in neurovascular regulation and its therapeutic potential in blood-brain barrier dysfunction.