Pericytes and Astrocytes Crosstalk: Understanding Perivascular Synergism at the BBB

Abstract

The Blood brain barrier (BBB) plays a critical role in maintaining brain homeostasis. Astrocytes (AC) lying adjacent to BBB endothelial cells (EC) have been reported to play a major role in ECs polarization and differentiation into a BBB phenotype. Pericytes (PC) have been reported to synthesize most elements of the basement membrane and provide structural support and vasodynamic capabilities to the brain microvasculature thus suggesting a more primary role in BBB differentiation than previously anticipated. Whether PC and AC modulate each other functions and activities (thus affecting the BBB) are still poorly understood. For this purpose we analyzed the conditioned media from human AC, PC and AC‐PC cultures and assessed the morphological changes in correspondingly treated human BBB EC. Analysis of culture media have shown that Ang‐1 (important for BBB TJ formation) was primarily released by PC rather than AC (release of Ang‐2) thus suggesting that PC play an important role in BBB maturation. Furthermore, PC induced AC redistribution (cytosol to membrane) of glut‐1, important for glucose transport across the BBB was seen. This suggests that PC can modulate AC functions thus affecting the BBB. In addition, EC culture in presence of PC and/or AC‐PC conditioned media (but not AC alone) reassembled in a capillary like structure formation. This suggests that PC also play a role during angiogenesis of brain microcapillary.