Introduction: The BBB is a natural barrier located in the endothelial cells of the cerebral microvessels (BMECs) that restricts exchanges between the bloodstream and the cerebral parenchyma. The integrity of the BBB is vital for preserving cerebral homeostasis, and neuroinflammatory processes alter the physical and/or metabolic properties of this barrier. The

brain pericyte, which shares a common basement membrane with BMECs, has been shown to be the major cell type involved in the induction and maintenance of BBB main features.

Methods: This presentation will review the role and intercellular interactions of human brain pericytes (hBP) with the cells of the neurovascular unit and particularly BMECs, based on the data generated within the lab in proteomics, cell physiology and studies of extracellular vesicles (EVs). 

Results: The protein pattern of hBP is modified once cocultured with BMECs and highlight a metabolic switch induced by BMECs on hBP. A stimulation of EV biogenesis is observed, indicating a potentiel need for a hBP-derived cell-cell communication through EVs. The mechanisms of interaction between BMECs and hBP-derived EVs are in favor a clathrin-coated pit- mediated endocytosis. Under inflammation, hBP-derived EVs exhibit a modified protein patern compared to untreated EVs, and induce a dysregulation of trans-endothelial electric resistance (TEER) on BMECs.

Discussion: Despite a former reputation of contaminant for BBB modeling in vitro, hBP remain of importance for maintainning the BBB phenotype, and BMECs also modulate the hBP functions

and developmental fates. This work opens perspectives on the role of hBP-derived EVs on the BBB features regulation.