Skip to main content
Fig. 4 | Fluids and Barriers of the CNS

Fig. 4

From: Membrane transporters control cerebrospinal fluid formation independently of conventional osmosis to modulate intracranial pressure

Fig. 4

Three transporters as key contributors of CSF secretion. a Illustration of the luminal ion transport proteins: NBCe2, NKCC1, NKA, and NHE1 in choroid plexus (grey) and their inhibitors DIDS/S0859, bumetanide, ouabain, and cariporide. CSF is shown in blue. b Representative time control experiment with ventriculo-cisternal perfusion in rats depicting the ratio of dextran (outflow/inflow) as a function of time with a solution change to an identical solution. c Quantification of the CSF production rate by ventriculo-cisternal perfusion in rats treated with intraventricularly-delivered inhibitors of NKCC1 (bumetanide, n = 7), NKA (ouabain, n = 6), NHE1 (cariporide, n = 5), NBCe2 (DIDS, n = 4) or control solution (n = 7) at solution change (grey box). d Summarized data obtained after 35–55 min of inhibitor/vehicle exposure, with statistical significance determined by one-way ANOVA, followed by Dunnett’s multiple comparisons test. Asterisks denote difference from control condition (vehicle), ***P < 0.001, NS = not significant. e Mean arterial blood pressure (AP) obtained during the ventriculo-cisternal perfusion experiments is illustrated before and after (55 min) intraventricular exposure of the pharmacological inhibitors. Statistical significance was determined with paired t-test. NS = not significant. f Illustration of IRDye 800 CW carboxylate dye injected in the right lateral ventricle shown in pseudo-colors superimposed on a white light image of the rat. The dye intensity is quantified as a function of time in the white box placed at lambda (left panel). Right panel illustrates a superimposed image of ventricular fluorescence on a white light image of a rat brain cut in the midsagittal plane after ended live imaging. The intensity scale is in arbitrary units. g Representative images of the dye content at T0.5 min and T5 min after placement in fluorescent scanner in control rats (Ctrl) or bumetanide-treated rats (Bum). h Live imaging of intraventricular IRDye 800 CW carboxylate dye following treatment with bumetanide (NKCC1 inhibition, n = 5), ouabain (NKA inhibition, n = 5), or S0859 (NBCe2 inhibition, n = 6) or control (vehicle) solution (n = 8). Inset: control: 0.12 ± 0.01 a.u. min−1, n = 7, vs. cariporide (NHE1 inhibition): 0.12 ± 0.02 a.u. min−1, n = 6. i Quantification of the dye flow rate determined from linear regression analysis of h over the 5 min with statistical significance determined by one-way ANOVA followed by Dunnett’s multiple comparisons test. Asterisks denote difference from control condition, ***P < 0.001, *P < 0.05

Back to article page