MODE OF DELIVERY MODULATES THE INTEGRITY OF THE MURINE CHOROID PLEXUS IN EARLY LIFE

Choroid plexuses (ChPs) are structures located within the brain ventricles that play a crucial role in neurodevelopment by regulating blood-cerebrospinal fluid exchanges, and by protecting the brain from peripheral insults. Although often considered functionally identical, the lateral (LV) and third (3V) ventricle ChPs occupy distinct anatomical locations, with distinct developmental timelines and roles in central processes. Interestingly, the individual roles of each ChP in early life remain poorly understood.
Among various perinatal exposures, caesarean delivery (CS) has been associated with changes in immune maturation and neurodevelopmental outcomes in humans and animal models. Given the critical role of the ChP barrier in early life, we investigated whether CS modulates the integrity of the LV and 3V ChPs by influencing their permeability, structure, and immune environment.
To test this hypothesis, we performed CS on pregnant female mice. At postnatal day 8 (P8), we assessed barrier integrity by analysing epithelial and endothelial architectures in LV and 3V ChPs, and evaluated their functional permeability by intra-liver injection of a fluorescent tracer (Cadaverine 1 kDa). Additionally, fresh tissue was extracted from P8 pups to assess ChP immune status through flow cytometry.
Overall, ChPs exhibited permeability-related changes across vascular and epithelial compartments, immune cell reorganisations, as well as consistent region-associated differences.
Our study shows, for the first time, that delivery mode is associated with functional, structural and cellular alterations of the ChP barrier in early life in mice. This highlights the critical role of the perinatal environment in the modulation of neonatal brain development.