Oxytocin Affects Barriergenesis in the Blood–Brain Barrier and the Blood–Cerebrospinal Fluid Barrier In Vitro Monoculture Transwell Models

The integrity of the brain's barrier systems-the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB)-is crucial for central nervous system homeostasis. Oxytocin (OXT), a neuropeptide with emerging peripheral roles, has been implicated in vascular function. This study investigates the hypothesis that OXT directly modulates the functional properties of the BBB and BCSFB via receptor-mediated mechanisms. Using Transwell monoculture in vitro models employing primary rat brain microvascular endothelial cells (BMECs) and choroid plexus epithelial cells (ChPlECs), we first confirmed biological purity and demonstrated constitutive expression of both OXT receptor (OXTR) and the receptor for advanced glycation end products (RAGE) in both cell types. Notably, OXTR and RAGE expression were significantly higher in choroid plexus cells compared to BMECs. Treatment with 800 nM OXT significantly increased transendothelial/epithelial electrical resistance (TEER) in both models, indicating enhanced barrier tightness, with a more rapid effect observed in the BCSFB model. However, paracellular permeability to Lucifer yellow remained unchanged. OXT treatment induced a transient increase in lactoperoxidase (LPO) levels in the conditioned medium at 24 h, followed by a decline at 48-72 h, coinciding with peak TEER values. These findings establish OXT as a potent modulator of cerebral barrier function, with the BCSFB exhibiting higher sensitivity. This novel role of OXT in barrier regulation extends its physiological repertoire and presents a potential therapeutic avenue for neurodevelopmental and neurodegenerative disorders associated with barrier dysfunction.