The Effect of Body Posture on Brain Glymphatic Transport

Abstract

The glymphatic pathway expedites clearance of waste, including soluble amyloid ␤ (A␤) from the brain. 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. Humans, as well as animals, exhibit different body postures during sleep, which may also affect waste removal. Therefore, not only the level of consciousness, but also body posture, might affect CSF-interstitial fluid (ISF) exchange efficiency. 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. To validate the MRI data and to assess specifically the influence of body posture on clearance of A␤, we used fluorescence microscopy and radioactive tracers, respectively. The analysis showed that glymphatic transport was most efficient in the lateral position compared with the supine or prone 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 optical imaging and radiotracer studies confirmed that glymphatic transport and A␤ clearance were superior in the lateral and supine positions. 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.

Cannula Implantation into the Cisterna Magna of Rodents

“…Acute CMc is suited for combination with 2-photon imaging, which provides detailed information about glymphatic activity within cortex to a depth of approximately 200 µm 1,2 . Importantly, acute CMc also affords the advantage of supporting unbiased MRI studies, where tracer distribution is followed dynamically, relative to an individual baseline image acquired before the initiation of CSF tracer injection 15,16,17 . For MRI, the dental needle used for CMc should be replaced by a borosilicate capillary (approximately 1 cm length, tip diameter of approximately 20 µm) attached to the PE tubing.…”

The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future

“…Here, using dynamic-contrast-enhanced MRI, it was found that there was lower interstitial solute retention and improved clearance when mice were placed in the lateral decubitus position compared to either prone or supine positions (39). Further, it was demonstrated that there was enhanced fluorescent CSF tracer influx to the cerebrum when mice were placed in the lateral position relative to being prone (39). Thus, it is clear that postural or gravitational factors also exert regulatory control over the glymphatic pathway.…”

Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

“…Following traumatic brain injury, reduced clearance of cortical interstitial solute was associated with motor and cognitive neurological deficits (26). While CSF-ISF exchange within the glymphatic pathway is improved by increased cerebral penetrating arterial pulsatility (27), the sleep state (20), and a lateral head position during sleep (28), none of these regulatory factors have yet been demonstrated to improve waste clearance in any of the above disease states. Consequently, a critical area of future glymphatic research is identification of novel mechanisms to control flow through this pathway with the goal of modifying diseases characterized by toxic extracellular solute accumulation.…”