Does exercise take out the trash?


The brain’s self-cleaning system is an under-appreciated and poorly understood feature that may potentially be the most important protagonist of damage inflicted by a bad lifestyle.

A lack of sleep and exercise may increase the risk of Alzheimer’s Disease. During sleep, the brain ‘cleans itself’. The architecture of the brain changes, the fluid spaces get larger, microglia do some pruning and astrocytes shift. If all goes to plan, we wake up refreshed. It is easy to see why sleep deprivation causes problems.

Exercise brings about neurogenesis (the birth of new brain cells) in mice and changes in hippocampal volume and blood flow, in humans. These are reason enough to explain its brain health-enhancing powers, but the recent discovery of the glymphatic system – a weird and wonderful waste-clearing pathway that had hitherto evaded detection – urges a second look at the effects of exercise.

The brain sits suspended in Cerebrospinal Spinal Fluid or CSF. CSF is the fluid that doctors analyse during a ‘spinal tap’. The brain substance is immersed in another, separate compartment of fluid, known as Interstitial Fluid or ISF.

Brain cells and glial cells release their waste into the ISF. It would appear that in order for this waste to be cleared away, it needs to move from the ISF into the CSF. The CSF carries waste away and disposes of it.

When the heart pumps blood around the body, the elasticity of the walls of blood vessels propagate the pulsatile wave generated by the heart. The wave has a peak that corresponds to the systolic blood pressure and a trough that corresponds to the diastolic blood pressure. (Blood pressure is measured with a reading of two numbers, the higher one is the systolic BP and the lower one the diastolic BP). The waveform dampens as the blood moves farther away from the heart. Blood vessels in the brain carry out ‘autoregulation’ to reduce the pulsatility even more. This protects the brain, since too big a waveform can cause harm .

A study on mice has shown that a large part of CSF-ISF exchange may be driven by the ‘pulsation’ of the blood vessels within the brain. Until this study is replicated in humans, its findings must be regarded as a theory of what might be happening within the human brain; nonetheless, it offers an interesting angle to the effects of exercise. Blood pressure rises during exercise, even if the exercise is relatively mild. It is possible that this mild rise in blood pressure, may slightly increase the pulsatility of blood flow through the brain. This rise may improve CSF-ISF exchange, helping the brain to clear out its garbage. In support of this, running seems to increase the rate at which Alzheimer’s disease related proteins are cleared away in mice. A human study has shown that exercising at a heart rate of 120bpm or more raises the pulsatility of blood flowing through the medial cerebral arteries. It seems that at this heart rate, cerebral autoregulation can't quite keep up.

A blood vessel pulsates better if it is supple. Vessels lose their elasticity with age and with a suboptimal lifestyle. This might explain why CSF-ISF exchange slows down with age. Both prediabetes and diabetes are associated with arterial ‘stiffness’. A meta-analysis of 42 randomized controlled trails concluded that aerobic exercise (but not resistance exercise) significantly improves arterial stiffness. The effect increases with intensity and is bigger if there is more stiffness to begin with.

There is a great deal more to be discovered about the glymphatic system and differing opinions and theories need to be reconciled. Its precise mechanism in humans is as yet unknown. If the theories are proven correct, they place exercise in a whole new light. When we go for a run to ‘clear the head’, we really may be taking out its trash!

References

  1. Iliff JJ, Wang M, Zeppenfeld DM, et al. Cerebral Arterial Pulsation Drives Paravascular CSF–Interstitial Fluid Exchange in the Murine Brain. The Journal of Neuroscience. 2013;33(46):18190-18199.

  2. Ogoh S, Fadel PJ, Zhang R, Selmer C, Jans Ø, Secher NH, Raven PB. Middle cerebral artery flow velocity and pulse pressure during dynamic exercise in humans. Am J Physiol Heart Circ Physiol. 2005 Apr;288(4):H1526-31.

  3. Herring A, Münster Y, Metzdorf J, Bolczek B, Krüssel S, Krieter D, Yavuz I, Karim F, Roggendorf C, Stang A, Wang Y, Hermann DM, Teuber-Hanselmann S, Keyvani K. Late running is not too late against Alzheimer's pathology. Neurobiol Dis. 2016 Oct;94:44-54.

  4. Ashor AW, Lara J, Siervo M, Celis-Morales C, Mathers JC. Effects of exercise modalities on arterial stiffness and wave reflection: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2014 Oct 15;9(10):e110034.

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