Fig. 1

Modulation of respiration, blood pressure and heart rate. The shaded graphs represent data obtained from animals used in the in vivo studies and injected with indocyanine green (ICG) (A, E, F, I, J). The other graphs (B–D, G, H, K, L) represent the animals from the ex vivo studies using fluorescent ovalbumin (AFO-647) as the CSF tracer. A–D To test how respiration effects CSF flow, rats were anaesthetised and spontaneously breathing (SB) or were mechanically ventilated to normocarbia (Normal) or to hypercapnia (Control). The peak circuit pressures of Normal and Control cohorts were significantly higher than that of SB. Similarly, the trough pressures were more negative in the SB group than either of the positive pressure ventilated groups (Normal and Control). C SB rats had significantly lower respiratory rates (around 50 breaths/min) than the Normal animals (set at a respiratory rate of 66 breaths/min) but matched that of the Control cohort. D The lower, physiological pCO₂ in the Normal group reflected the circuit pressure (used as an indirect measure of intrathoracic pressure) and respiratory rate. E–H To test the effect of blood pressure on CSF flow, phenylephrine infusions were administered to induce hypertension. E, G Sustained mean arterial pressure (MAP) and F, H pulse pressure of approximately 140 mmHg and 80 mmHg respectively over 20 min were achieved. These values were twice that of controls. I, K To investigate the effects of heart rate on CSF flow, tachycardia was achieved by electrically pacing animals to 500 bpm. These animals had heart rates approximately 50% higher than the mechanically ventilated controls, without any blood pressure differences, demonstrated in J, L. Two tailed Student’s t-test, **p < 0.01, ***p < 0.001, ****p < 0.0001. All error bars are expressed as ± SD, n = 6/7 rats