For example, cerebral hemodynamics and intracranial pressures are highly influenced by body posture ( Schneider et al., 1993 Brosnan et al., 2002 Kose and Hatipoglu, 2012) and this in turn could affect glymphatic pathway transport. Therefore, not only arousal level, but also body posture, might affect the brain's waste removal efficiency. Humans, as well as animals, exhibit different body posture during the awake and sleep states. The enlarged interstitial space volume during deep-wave sleep lowers the overall resistance to paravascular inflow, resulting in a sharp increase in CSF-ISF exchange and convective transport of waste solutes toward paravascular spaces surrounding large caliber cerebral veins for ultimate clearance via cervical lymphatic vessels ( Xie et al., 2013). This finding is in agreement with other studies demonstrating synaptic plasticity and down-selection of synapses in association with sleep ( Bushey et al., 2011 Cirelli and Tononi, 2015).
During sleep or anesthesia, the brain interstitial space volume expands significantly compared with the awake state ( Xie et al., 2013). Subsequent studies showed that glymphatic transport is controlled by the brain's arousal level ( Xie et al., 2013). This so-called “glymphatic” pathway facilitates the clearance of interstitial waste from the brain parenchyma ( Nedergaard, 2013). In recent studies, we reported on the brainwide paravascular pathway, in which a large proportion of subarachnoid CSF circulates through the brain parenchyma via para-arterial spaces, exchanges with the interstitial fluid (ISF), and exits along para-venous pathways ( Iliff et al., 2012). Although our finding awaits testing in humans, we speculate that the lateral position during sleep has advantage with regard to the removal of waste products including Aβ, because clinical studies have shown that sleep drives Aβ clearance from the brain. The major finding of our study was that waste, including Aβ, removal was most efficient in the lateral position (compared with the prone position), which mimics the natural resting/sleeping position of rodents. We investigated the influence of body posture on brainwide transport of inert tracers of anesthetized rodents. Animals exhibit different body posture during the awake and sleep states, which might affect the brain's waste removal efficiency. SIGNIFICANCE STATEMENT The rodent brain removes waste better during sleep or anesthesia compared with the awake state. We propose that the most popular sleep posture (lateral) has evolved to optimize waste removal during sleep and that posture must be considered in diagnostic imaging procedures developed in the future to assess CSF-ISF transport in humans. The optical imaging and radiotracer studies confirmed that glymphatic transport and Aβ clearance were superior in the lateral and supine positions. In the prone position, in which the rat's head was in the most upright position (mimicking posture during the awake state), transport was characterized by “retention” of the tracer, slower clearance, and more CSF efflux along larger caliber cervical vessels. The analysis showed that glymphatic transport was most efficient in the lateral position compared with the supine or prone positions. To validate the MRI data and to assess specifically the influence of body posture on clearance of Aβ, we used fluorescence microscopy and radioactive tracers, respectively. We used dynamic-contrast-enhanced MRI and kinetic modeling to quantify CSF-ISF exchange rates in anesthetized rodents' brains in supine, prone, or lateral positions. Therefore, not only the level of consciousness, but also body posture, might affect CSF–interstitial fluid (ISF) exchange efficiency. Humans, as well as animals, exhibit different body postures during sleep, which may also affect waste removal. Transport through this pathway is controlled by the brain's arousal level because, during sleep or anesthesia, the brain's interstitial space volume expands (compared with wakefulness), resulting in faster waste removal. The glymphatic pathway expedites clearance of waste, including soluble amyloid β (Aβ) from the brain.
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