Variation between sleep and wakefulness
In the comparative studies undertaken on sleeping and awake mice by Xie et al. [128] there were differences in clearance and in interstitial fluid volume in the two physiological states. In these studies, inulin was used as the marker solute for perivascular clearance and the real-time iontophoresis method [74] was used to assess the volume. Briefly Xie et al. [128] found that, in the change from sleep to wakefulness, ISF volume decreased by 1.6-fold, the rate constant for efflux of inulin decreased 2.7-fold and from these values it could be estimated that inulin clearance decreased 4.3-fold (see Section 2.4 in [146]). Changes in the rate of access into the parenchyma of markers added to CSF and the discrepancies between the results of Xie et al. and of Gakuba et al. [147] are discussed briefly in.10
As discussed in [146] it is at present unclear whether any change in perivascular clearance of inulin in the transition from sleep to wakefulness is a consequence of the change in ISF volume in the parenchyma or some other effect. There are other possible effects of sleep versus wakefulness that might plausibly alter the clearance, e.g. changes in the shape or volume of either the perivascular spaces or the glial endfeet surrounding them.