Health Science Reviews

by Jessica Garlick

You have probably heard about the elusive glymphatic system- the waste clearance system of the brain- since its recent identification has caused great excitement in the scientific community. The current literature indicates that the glymphatic system is affected by your state of arousal- whether you are awake or asleep- and is conveniently more active while you sleep.

During sleep the interstitial space, a vital component of the glymphatic system, increases in size (volume) and there’s less resistance within the blood vessels of the brain which allows for more effective exchange, including waste removal, to take place. Lee et al. (2015) wanted to determine if the body’s position during sleep influences the rate of waste removal by increasing or decreasing the rate of Cerebrospinal fluid (CSF)-Interstitial fluid (ISF) exchange. To do this, anaesthetised rats in different positions were analysed using “dynamic-contrast-enhanced MRI and kinetic modelling” and these results were validated using fluorescence microscopy and radioactive tracers in mice, where clearance or retention of the waste product, amyloid beta, was monitored.

Rats lying on their right sides- a lateral position- had greater clearance than in the other positions. This is fantastic news for most of us as lying on your side is the most popular sleep position and Lee et al. (2015) believes this may be an evolutionary derived behaviour to aid this clearance system. Rats lying on their backs- supine position – also showed improved clearance over rats that were lying on their stomachs- prone position- whose heads were positioned to mimic that of an awake state. It makes sense that their clearance was lower than the other groups as it is already known that the glymphatic system is less effective when you are awake. You may be wondering what happens to your glymphatic system if you change positions during sleep, as most of us do, and this was discussed as a limitation to this study since rats remained in the same position throughout the experiment. Unfortunately, further studies would be needed to answer that question.

So why was the glymphatic system more efficient at waste removal when in a lateral sleeping position? The answer to this question is very complex and involves many factors, including: breathing pattern, heart rate and compression of blood vessels and nerves. For example, if the vena cava, a large vein that feeds into your heart, is compressed then cardiac stroke volume would decrease, which would decrease the arterial pulsatility, a driving force for clearance, therefore lowering the efficiency of the glymphatic system. Furthermore, a known natural response to decreased stroke volume is a higher sympathetic response (release of adrenaline) and adrenaline is already known to inhibit the glymphatic system.
When lying on your stomach, there’s a high probability of compressing nerves and blood vessels, like the vena cava, and this study purposely didn’t relieve the pressure on the abdomen.
However, when you lie on your side, glymphatic clearance improves because the vagus nerve is stimulated, which increases parasympathetic signalling (opposes sympathetic signalling), which increases stroke volume, thus increases pulsatility, and inhibiting a sympathetic response.

Although posture affects respiratory and heart rates, which affect the pressure that drives CSF flow and thus affects glymphatic clearance, there weren’t significant statistical differences between groups in this study. Ketamine and xylazine mix were used to anaesthetise the rodents since it has the least respiratory depressant effects compared to other anaesthetics and there weren’t differences in respiratory rates of rodents prior to the experimental readings. However, rapid-eye-movement sleep may be supressed and natural sleep is much more complex than anesthetised ‘sleep’.  Lee et al. (2015) didn’t monitor blood gases and think there could have been reduced vascular pulsatility and resistance owing to reduced respiration efficiency during sleep, which may explain the differences observed.

So overall, what does this study show? The right lateral sleeping position was the optimal position for amyloid beta (waste) removal in rodents. Head position affects glymphatic activity in rodents and is “an important factor to consider in future diagnostic tests of glymphatic activity”. Lee et al. (2015) believe that head position would aid predictive outcomes from shunt surgery in normal pressure hydrocephalus (NPH) when taking sleep position (especially head position) into consideration while conducting radionuclide cisternography for its diagnosis. Lee et al. (2015) clearly states that this experiment needs to be done in a human context, acknowledge the limitations of this study and highlight areas where more research is needed.

References

Lee H, Xie L, Yu M, Kang H, Feng T, Deane R, et al. The effect of body posture on brain glymphatic transport. J Neurosci. 2015;35(31):11034–44.