Brain Waste Removal System Works Best While Sleeping on Side

Helene Benveniste, MD, PhD Professor of Anesthesiology and Radiology Vice Chair for Research, Department of Anesthesiology Stony Brook Medicine, Stony Brook Interview with:
Helene Benveniste, MD, PhD
Professor of Anesthesiology and Radiology
Vice Chair for Research, Department of Anesthesiology
Stony Brook Medicine, Stony Brook NY

Medical Research: What is the background for this study?

Dr. Benveniste: The ‘glymphatic’ pathway is a part of the brain and is responsible for removal of waste products and excess fluid that built up especially during wakefulness. The concept was introduced by Nedergaard’s team in 2012 from University of Rochester. Importantly it has been shown to remove waste products such as soluble amyloid beta and tau protein which build up excessively in the brain of subjects afflicted with Alzheimer’s disease. The glymphatic system has been studied in detail in animal models (not yet humans) and actually is a brain-wide pathway which runs along (i.e. on the outside) of all vessels in the brain and connects to the space around the brain cells (referred to as the interstitial fluid (ISF) space). The outer part of the glymphatic network ‘tube’ is bordered by a certain type of brain cells so-called ‘astroglial’ cells which are arranged in a special way so that their endfeet cover >97% of the surface of all brain vessels. One can think of this as if the astroglial cell’s ‘endfeet’ are arranged as a donut shaped tube around all the vessels. On the astroglial endfeet there are special water channels (aquaporin-4 water channels) which are critical for how efficiently the glymphatic system can get rid of waste because it allows water to move fast through the brain tissue so as to ‘flush’ waste products out efficiently. The small gap between the astroglial endfeet also act like a ‘sieve’ so that only waste products of a certain size can access the entire pathway. Cerebrospinal fluid (CSF) circulates into the glymphatic pathway from the surface of the brain along the arteries which dives directly from the surface into the deeper part of the brain; and ultimately enters the space around the brain cells; and sweeps through it and thereby mixes with the interstitial fluid of the brain which contains waste products. The CSF-ISF mix with the waste products is then flushed out on the other ‘side’ along the veins and ultimately ends up in lymph vessels in the body and then in the blood.

It has been shown that the glymphatic pathway removes brain waste more efficiently in a state of ‘unconsciousness’ e.g. sleep or anesthesia when compared to wakefulness. Given this intriguing finding i.e. that sleeps seems to affect the waste clearance from the brain we thought that the next to look at was sleeping positions. We did these studies in anesthetized rodents.

Medical Research: What are the main findings?

Dr. Benveniste: The main findings of our study was that the lateral/side position is the body position which appears to move brain waste (including amyloid beta) most efficiently during unconsciousness when compared to prone (on the stomach with the head higher and/or in the supine position). We also observed that in prone position (the position which renders the glymphatic pathway least efficient in regards to waste clearance) cerebrospinal fluid is diverted away from the brain towards the spine and larger structures on the neck such as the carotid sheet. This is probably why waste clearance is less efficient in that position.

Medical Research: What should clinicians and patients take away from your report?

Dr. Benveniste: It is too early to provide recommendations based on our study in rodents. The next step is to study the glymphatic pathway in human brain. However, there are diagnostic radiological tests in the clinical arena that use the same approach i.e. radioactive tracers are injected into the spinal CSF and the distribution of the tracer is followed into the brain over time. These tests are referred to as ‘radionuclide cisternography’ and are used in many medical centers to evaluate patients for CSF leaks or for hydrocephalus or benign intracranial hypertension. Often these tests take a long time and the patients have to have their brains scanned several times over 2-3 days. Often these tests are ‘inconclusive’ and one reason could be that sleep quality or sleep position (between scans) are never taken into consideration. Same issue applies to tests where CSF biomarkers are being collected from patients for various diagnostic purposes including alzheimer’s disease. The CSF content of substances may not only be dependent on sleep but also body position during sleep.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Benveniste: We are working with other colleagues to study how the system can be controlled and maintained over a lifetime so as to maximize waste clearance and to prevent disease. Also, we are working on developing diagnostic platforms and tools to quantify glymphatic transport and clearance of  brain waste which will be essential for interpretation of future data.


Hedok Lee, Lulu Xie, Mei Yu, Hongyi Kang, Tian Feng, Rashid Deane, Jean Logan, Maiken Nedergaard, and Helene Benveniste. The Effect of Body Posture on Brain Glymphatic Transport. Journal of Neuroscience, July 2015 DOI: 10.1523/JNEUROSCI.1625-15.2015

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Helene Benveniste, MD, PhD (2015). Brain Waste Removal System Works Best While Sleeping on Side 

Last Updated on August 8, 2015 by Marie Benz MD FAAD