Fig. 6

Sensitivity analysis for model 2. Steady-state conditions refer to the sensitivity measured at 10 h of simulation. The x axis in the heatmap plots specifies the sensitivity inputs. Y axes show the normalized sensitivity of venous, arterial, and lymphatic fluid obtained by varying the values of S100B in the compartments indicated by the numbers. The values of the outputs were integrated over time. We used global sensitivity analysis to interpret the impact of S100B levels in various organs on venous, lymphatic, and arterial biomarker levels. The key for the numbers at the bottom of each panel is 1: Venous blood; 2: Vascular compartment brain; 3: Vascular compartment adipose; 4: Vascular compartment gut; 5: Vascular compartment muscle; 6: Interstitium adipose; 7: Interstitium brain; 8: Interstitium gut; 9: Interstitium muscle; 10: Arterial blood; 11: Central lymph. When the brain is isolated from the periphery, and the only source of S100B available is the content of peripheral organs (top panel), the gut is the chief controller of body fluids S100B. However, when a communication brain to periphery is established via glymphatic drainage, the brain becomes the most influential organ for circulating S100B. This remains true after BBBD and the opening of the communication between the astrocyte content of S100B and the interstitium in the brain. For the brain interstitium S100B, in this simulation we used 10 ng/ml a concentration between CSF values (~ 3 ng/ml) and the measured interstitial value reported in [55]. See also Additional file 1: Fig. S1, Additional file 2: Fig. S2, Additional file 3: Fig. S3