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The Effect of Body Posture on Brain Glymphatic Transport.
J Neurosci. 2015 Aug 05; 35(31):11034-44.JN

Abstract

The glymphatic pathway expedites clearance of waste, including soluble amyloid β (Aβ) 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 Aβ, 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 Aβ 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.

SIGNIFICANCE STATEMENT

The rodent brain removes waste better during sleep or anesthesia compared with the awake state. Animals exhibit different body posture during the awake and sleep states, which might affect the brain's waste removal efficiency. We investigated the influence of body posture on brainwide transport of inert tracers of anesthetized rodents. 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. 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.

Authors+Show Affiliations

Department of Anesthesiology, Department of Radiology, and.Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14627.Department of Anesthesiology.Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14627.Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794.Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14627.Department of Radiology, New York University Langone Medical Center, New York, New York 10016, and.Center for Translational Neuromedicine, University of Rochester, Rochester, New York 14627.Department of Anesthesiology, Department of Radiology, and Helene.Benveniste@stonybrookmedicine.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26245965

Citation

Lee, Hedok, et al. "The Effect of Body Posture On Brain Glymphatic Transport." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 35, no. 31, 2015, pp. 11034-44.
Lee H, Xie L, Yu M, et al. The Effect of Body Posture on Brain Glymphatic Transport. J Neurosci. 2015;35(31):11034-44.
Lee, H., Xie, L., Yu, M., Kang, H., Feng, T., Deane, R., Logan, J., Nedergaard, M., & Benveniste, H. (2015). The Effect of Body Posture on Brain Glymphatic Transport. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 35(31), 11034-44. https://doi.org/10.1523/JNEUROSCI.1625-15.2015
Lee H, et al. The Effect of Body Posture On Brain Glymphatic Transport. J Neurosci. 2015 Aug 5;35(31):11034-44. PubMed PMID: 26245965.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Effect of Body Posture on Brain Glymphatic Transport. AU - Lee,Hedok, AU - Xie,Lulu, AU - Yu,Mei, AU - Kang,Hongyi, AU - Feng,Tian, AU - Deane,Rashid, AU - Logan,Jean, AU - Nedergaard,Maiken, AU - Benveniste,Helene, PY - 2015/8/7/entrez PY - 2015/8/8/pubmed PY - 2015/11/6/medline KW - CSF KW - brain KW - posture KW - sleep KW - unconsciousness KW - waste removal SP - 11034 EP - 44 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 35 IS - 31 N2 - UNLABELLED: The glymphatic pathway expedites clearance of waste, including soluble amyloid β (Aβ) 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 Aβ, 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 Aβ 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. SIGNIFICANCE STATEMENT: The rodent brain removes waste better during sleep or anesthesia compared with the awake state. Animals exhibit different body posture during the awake and sleep states, which might affect the brain's waste removal efficiency. We investigated the influence of body posture on brainwide transport of inert tracers of anesthetized rodents. 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. 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. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/26245965/The_Effect_of_Body_Posture_on_Brain_Glymphatic_Transport_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=26245965 DB - PRIME DP - Unbound Medicine ER -