Three-dimensional culture conditions differentially affect astrocyte modulation of brain endothelial barrier function in response to transforming growth factor β1

摘要: Blood-brain barrier (BBB) function is regulated by dynamic interactions among cell types within the neurovascular unit, including astrocytes and endothelial cells. Co-culture models of BBB typically involve seeded on two-dimensional (2D) surfaces, which recent studies indicate cause to express a phenotype similar that reactive in situ. We hypothesized culture conditions would differentially affect their ability modulate vitro. Brain cells were grown alone or co-culture with astrocytes. Astrocytes either as conventional monolayers, collagen-based gel allows them grow three-dimensional (3D) construct. viable 3D conditions, displayed marked reduction expression glial fibrillary acidic protein (GFAP), suggesting reduced activation. Stimulation transforming growth factor (TGF)β1 decreased transendothelial electrical resistance (TEER) claudin-5 co-cultures, whereas treatment absence was without effect. The effect TGFβ1 TEER significantly more pronounced cultured compared 2D These results demonstrate astrocyte brain function, suggest direct relationship between gliosis permeability. Moreover, these potential importance physiologically relevant vitro modeling disease processes unit.