The blood-brain barrier (BBB) restricts the transport of substances between vasculature and brain and BBB permeability is important data for the development of new drugs. However, it is not known whether microglia have roles in the regulation of BBB permeability. In this study, we tried to develop an in vitro BBB model including microglia. We also investigated the difference in the effects of microglia on BBB permeability caused by activation state.
Co-existence of resting microglia (i.e., non-stimulated microglia) with astrocyte in the brain side of BBB model significantly increased the transendothelial electrical resistance (TEER) and the expression level of tight junction proteins. Conversely, co-existence of activated microglia (i.e., LPS-stimulated microglia) with astrocyte significantly decreased the TEER and the expression level of tight junction proteins. These results suggest that microglia affect BBB permeability in both of physiological and pathological conditions. Moreover, addition of resting microglia significantly increased L-Glu transporter functions via increasing the expression level of GLAST and GLT1 proteins in endothelial cells. Conversely, addition of activated microglia significantly decreased L-Glu transporter functions. These results suggest that L-Glu transporters in the BBB have significant roles in the regulation of L-Glu concentration inside the brain and microglia also affect their functions in both of physiological and pathological conditions..
In summary, we developed the novel BBB model including microglia. This model is reflecting the changes in BBB barrier functions under physiological and pathological conditions