Fig. 3

TRPV4 activity modulates ICP and CSF production in vivo. A Schematic illustrating the cranial window (shown as a dotted circle) into which the ICP probe is positioned, LV; lateral ventricle. B ICP as a function of time upon infusion of control solution, n = 5 (black) or TRPV4 inhibitor-containing solution, n = 5 (RN; purple) shown as 5 min average values normalized to the baseline. Inset, initial ICP, n = 10. C Summarized changes in ICP with control solution (black) and TRPV4 inhibitor-containing solution after 1.5 h. D Schematic of the VCP method used to determine the CSF production rate. E Representative time course of the dextran ratio (outflow/inflow) with a mock solution change with control solution (indicated with a grey bar). Inset, average CSF production rate, n = 7. F CSF production as a function of time. Data normalized to the last four samples before solution change to either the control solution, n = 7 (black), the TRPV4 activator GSK, n = 6 (green), or the TRPV4 inhibitor RN, n = 6 (purple). G Summarized CSF production rates in % of control after exposure to vehicle (black), TRPV4 activation (green) and TRPV4 inhibition (purple). H Correctly targeted dye delivery in mid-saggital sections of a rat brain. I A representative image of a rat after injection of IRDye 800CW carboxylate dye (superimposed pseudo-color). The square placed in line with lambda indicates the area of dye content quantification. J Representative images obtained at t = 0.5 (t_0.5) and t = 5 (t₅) min in control solution (left) or upon TRPV4 inhibition (RN; right). K The dye intensity normalized to that obtained in the first image and plotted as a function of time representing flow rate for control, n = 5 (black), TRPV4 activation, n = 6 (GSK, green) and TRPV4 inhibition, n = 6 (RN, purple). L Quantification of the dye intensity (flow rate) determined from linear regression in K over the 5 min. time window from control (black), TRPV4 activation (green) and TRPV4 inhibition (purple). Statistical evaluation with Student’s t-test (C) or one-way ANOVA with Dunnett’s post hoc test (F and K) *P < 0.05; **P < 0.01; ***P < 0.001