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DEEP DIVE

The brain and its nighttime waste disposal team

Your brain produces large amounts of waste products (cellular detritus; remnants of dead cells, proteins and much more) that need to be cleared away to keep your brain healthy.

One example of harmful waste is newly formed proteins that won’t work properly because they do not have the correct three-dimensional shape. Left in place, these misfolded proteins will clump together into aggregates (clusters). Protein clusters of this kind have been linked to a number of neurodegenerative disorders, including Alzheimer's disease. That is why it is so very important – in fact vital – to rid the brain of waste products. We’re not just talking about a few milligrams here. Experts estimate that grams of the stuff build up in our brains every day. Proper disposal is a daunting task.

Waste management – but how?

Everywhere but the brain, waste is cleared by lymphatic vessels that run through the body like a network of hydraulic pipes. This network does not serve the brain. The lymphatic system stops outside the brain at the meninges. Waste clearance in the brain is organized by the so-called glymphatic (glial-lymphatic) system. The glymphatic system is a network of very fine channels arranged around the blood vessels in the perivascular space. Cerebrospinal fluid (CSF) flows here, propelled by the wave-like motions triggered by the pumping of your heart. The CSF picks up the waste. The waste travels through the perivascular space into your lymphatic system and then into your bloodstream, eventually reaching your liver and kidneys for processing or elimination.

Why does the brain need a special waste disposal system?

Brain cells do not break down most of their waste themselves. Recent research indicates that the brain limits itself to flushing out harmful substances, leaving the rest of the work to the other organs whose job it is anyway. The brain’s unique drainage system is yet another demonstration of the exceptional nature of the brain and just one of the many ways it is special among organs.

Waste disposal while you sleep

Experiments have shown that, when we are awake, the perivascular space is tiny. Not a lot of waste-flushing can be going on in there. But when we sleep, the interstitial (between-cells) space enlarges and perivascular fluid flow can happen. These observations show that waste disposal from the brain mainly takes place at night. And that’s one more reason why sleep is so important to keep your central nervous system functioning smoothly. More food for thought: animal studies have shown that sleep deprivation resulted in greater accumulation of waste products – including amyloids, the protein particles responsible for dementia.

 

  • 1. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012 Aug 15; 4(147): 147ra111. doi: 10.1126/scitranslmed.3003748.

    2. Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The Glymphatic System: A Beginner's Guide. Neurochem Res. 2015 Dec; 40(12): 2583–99. doi: 10.1007/s11064-015-1581-6. Epub 2015 May 7. Review.

    3. Raper D, Louveau A, Kipnis J. How Do Meningeal Lymphatic Vessels Drain the CNS? Trends Neurosci. 2016 Sep; 39(9): 581–586. doi: 10.1016/j.tins.2016.07.001. Epub 2016 Jul 25. Review.

    4. Simon MJ, Iliff JJ. Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease. Biochim Biophys Acta. 2016 Mar; 1862(3): 442–51. doi: 10.1016/j.bbadis.2015.10.014. Epub 2015 Oct 22. Review.

    5. O'Donnell J, Ding F, Nedergaard M. Distinct functional states of astrocytes during sleep and wakefulness: Is norepinephrine the master regulator? Curr Sleep Med Rep. 2015 Mar; 1(1): 1–8. Epub 2015 Jan 29.

    6. Spektrum der Wissenschaft Kompakt: Schlafen und Träumen. Heidelberg 2015.

    7. Maiken Nedergaard, Steven A. Goldman: Nächtliche Gehirnwäsche. Spektrum der Wissenschaft 12/2016.

    8. Spektrum der Wissenschaft Dossier: Gehirn und Geist, Heidelberg 2012.

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