ObjectiveThis study aimed to assess the effect of transcranial direct current stimulation (tDCS) and exercise on blood-brain barrier (BBB) permeability in humans as assessed through the quantification of the salivary protein biomarker S100B. It was hypothesized that active tDCS would induce a significant increase in salivary S100B concentration when compared with sham stimulation and no stimulation. It also was hypothesized that the increase in salivary S100B concentration would be greater after active tDCS and exercise than after tDCS or exercise alone. Materials and MethodsA total of 13 healthy adults (five male, eight female), ranging in age from 21 to 32 years, underwent three experimental conditions (active tDCS, sham tDCS, inactive control). To assess exercise- and tDCS-induced changes in BBB permeability, S100B in saliva was measured. Saliva samples were taken before tDCS, after tDCS, and immediately after a ramped cycling time-to-exhaustion (TTE) task. Active tDCS involved the application of anodal stimulation over the primary motor cortex for 20 minutes at 2 mA. ResultsS100B concentrations in the control condition did not differ significantly from the active condition (estimate = 0.10, SE = 0.36, t = 0.27, p = 0.79) or the sham condition (estimate = 0.33, SE = 0.36, t = 0.89, p = 0.38). Similarly, S100B concentrations at baseline did not differ significantly from post-intervention (estimate = −0.35, SE = 0.34, t = −1.03, p = 0.31) or post-TTE (estimate = 0.66, SE = 0.34, t = 1.93, p = 0.06). ConclusionsThis research provides novel insight into the effect of tDCS and exercise on S100B-indicated BBB permeability in humans. Although the effects of tDCS were not significant, increases in salivary S100B after a fatiguing cycling task may indicate exercise-induced changes in BBB permeability.