Figure 6.

Brain chip metabolite production is altered by coupling to the BBB. (a–c) The mean production/consumption of glutamate (Glu) (a), glutamine (Gln) (b) and GABA (c) depends on the substrate available for the neuronal culture. The neuronal cultures in the brain chip were given different C₁₃-labeled metabolic substrates that are essential for GABA production. The labeled substrates arrived directly to the brain chip (uncoupled system, unfilled) and through the vasculature of BBB (linked system, black). Gln *P values for all comparisons versus the coupled NVU system <0.0001; GABA *P values: glucose (Glc) = 0.0124, lactate (Lac) = 0.0073, pyruvate (Pyr) = 0.0048, (Supplementary Table 1a). Error bars are s.e.m., N = 3 for uncoupled systems and 5 for coupled systems, significance calculated with one-way ANOVA, Bonferroni post-test, (Supplementary Table 1a). (d) Theoretical metabolic flux balance analysis of the synaptic cleft. GABA exchange is shown as a function of the uptake of glucose or equal amounts of lactate and pyruvate in the presence or absence of metabolites in parentheses. All fluxes are reported as μmol·g wet brain⁻¹·min⁻¹.