Glymphatic System - Newly discovered system needs attention!

Glymphatic System, what is it? We have all heard of the Lymphatic system and its role in the body, but one rarely covered bodily system is the Glymphatic System. It sounds so similar one would think it's just a mispronunciation of the word ‘Lymphatic’. But, in fact, it’s an entirely different series of processes which we will break down in sequence below.

The Glymphatic System is a newly discovered macroscopic waste clearance system that utilizes a complex formation of what is called ‘Perivascular Tunnels’ that enable back and forth movement of fluid exchange, and the promotion to eliminate soluble proteins and metabolites from the central nervous system. It's more than just a waste clearance system for the brain though, its network of tasks expands far and wide….

Facilitating the delivery of nutrients to the brain

The Glymphatic system, while also aiding in waste removal, delivers across the brain, its vital nutrients:

• Glucose.
• Lipids.
• Amino Acids.
• Growth Factors.
• Neuromodulators (Neurotransmitters diffused through neural tissue).

It is most dominant during sleep!

This intricate system is predominantly disengaged during awake states, and most active when we are in a state of rest and or asleep. This reconfirms the idea around the requirement of sleep for humans and animals alike where science previously found no reason why we were required to sleep but that we did it anyway. This gives birth to the concept that unconsciousness is required for the Neurotoxins and waste clearance to occur including that of B-Amyloid. Excessive accumulation of B-Amyloid contributes to the formation of Plaque matter between nerve cells in the brain that is quickly becoming a hallmark for the development of Alzheimer’s disease.

Poor Function of the Glymphatic System is now being linked as a strong correlation to:

• Pathology of neurodegenerative disorders.
• Behavioural issues.
• Traumatic Brain Injury.
• Strokes.

So, the flushing movement of this fluid to deliver like a tide formation our nutrients required for brain function and also the ability to flush waste is extremely important but what makes up this fluid though?

How does the circulation work?

The brain and spinal cord have tidal flushes of Cerebral Spinal Fluid (CSF), the brain itself consists of four fluid dominant compartments.

1. Cerebral Spinal Fluid. 10%
2. Interstitial Fluid. 12-20%
3. Intracellular Fluid.60-80%
4. Blood Vasculature. 10%

Blood is separated from the rest of the CSF and the Interstitial fluids by what is called the ‘Blood-Brain Barrier’, and this separation is done via the support network of tight junctions, much like the tight junction proteins of our gut wall, it's designed to stop the macromolecules moving freely from the blood and into the brain Parenchyma. The Parenchyma is the functional tissue of the brain, consisting of both Glial Cells and Neurons.

What can impact and influence the Glymphatic system?

Circadian Rhythm –

The Mammalian Circadian Rhythm or day/night clock that governs our sleep and wake cycle of the body is mediated by the suprachiasmatic nucleus the Master of the body’s Hierarchal circadian system located in the Hypothalamus of our brain. But what we have also seen is that the Choroid Plexus also maintains the health of the Master Clock through the production of cerebral spinal Fluid production, the tidal action of the CSF controls the temperature environment as well waste movement in and out of the brain. The signalling of the Hypothalamus is hypersensitive to temperature, if poor Glymphatic function is present, then our circadian rhythm can be vastly disturbed through poor hypothalamic signalling.

Be it that CSF’s role is to flush out toxic waste and metabolite clearance from the brain and spinal cord through to the lymphatic. We mentioned above that the Glymphatic is most active in its supporting function while we are asleep and this is due to the activity of the Choroid Plexus mediating our circadian clock along with our Hypothalamic Master the suprachiasmatic nucleus. We can’t stress how important it is to have rest and good rest at that!

Injury and posture –

Above we mentioned how the CSF helps to regulate waste clearance, removal of B-Amyloid Plaque and also our sleep state among many many other functions but did you also know that because of the way it moves down and up the spinal cord and into the brain, that this movement can be impaired by structural variables? Yep, the function can be impaired from injury, poor posture stance, long term exposure to positions that can stagnate the flow of CSF and affect the temperature control of the brain and Hypothalamus[1].

BBB –

Our Blood-Brain Barrier (BBB) is much like that of our intestinal wall, tightly knitted together to allow micronutrients through but not macromolecules. The Brain capillary endothelial cells form the blood-brain barrier and allow transportation of essential amino acids transferring Neutral amino acids from extracellular fluid to the endothelial cells and into circulation for nourishment. However, much like our gut tight junction network, the tight junction network of the blood-brain barrier can become too permeable and allow larger particles through causing a higher demand for the Glymphatic systems flushing of toxic and waste accumulation meaning that these wastes can accumulate and contribute to many behavioural, mood and memory disturbances. 

Symptoms of an Impaired Glymphatic system [2]…

• Poor memory function, losing train of thought.
• Poor mood and or behavioural problems.
• Waking up feeling lethargic.
• Wanting to sleep early in the day.
• Lack of enthusiasm.
• Diagnosis of neural disease states, Alzheimer’s, Parkinson’s, Dementia.
• Hormonal dysregulation.
• Poor sleep patterns, circadian rhythm is off. Cortisol dysregulation.

Looking after your Glymphatic System

Taking care of this system is so important for the cascade of functions that it contributes to our health and mental wellbeing too so what do we need to do to nourish and care for it?

• If you have poor sleep hygiene, not going to bed early enough, being overstimulated by caffeine or electronics before bed can throw out the natural cortisol decline that puts us into a good sleep state. Eliminate obvious factors impacting your sleep.
• Take care of yourself structurally – Stretch, massage and work with structural manipulation modalities like a physio or chiro if you have stiffness, poor posture or long-term injury to your neck and back.
• Amino acids - Tryptophan, Tyrosine, Histidine, and Arginine are required by the brain for the synthesis of our neurotransmitters and neuromodulators. Interestingly, when we talk about mood and behaviour, one point to make note of is that our Tryptophan, Tyrosine and also Serotonin plasma levels can be impacted when uptake is competed for by higher levels of Tyrosine, Phenylalanine, leucine, Isoleucine and Valine. This is often why Matt will suggest not drinking branch chain amino all day as it can affect our uptake and total plasma levels of serotonin and Tryptophan in the brain causing poor mood. (3) Total Essential amino Acid supplements that include the amino acid Tyrosine seem to counteract this effect.

References

1. 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), 11034–11044. https://doi.org/10.1523/JNEUROSCI.1625-15.2015
2. García-Aviles JE, Méndez-Hernández R, Guzmán-Ruiz MA, Cruz M, Guerrero-Vargas NN, Velázquez-Moctezuma J, Hurtado-Alvarado G. Metabolic Disturbances Induced by Sleep Restriction as Potential Triggers for Alzheimer's Disease. Front Integr Neurosci. 2021 Sep 3;15:722523. doi: 10.3389/fnint.2021.722523. PMID: 34539357; PMCID: PMC8447653.
3. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines. Choi S1, Disilvio B, Fernstrom MH, Fernstrom JD. 2013 Nov;45(5):1133-42. doi: 10.1007/s00726-013-1566-1. Epub 2013 Aug 1.
4. 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. PMID: 25947369; PMCID: PMC4636982.
5. Mendelsohn AR, Larrick JW. Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases. Rejuvenation Res. 2013 Dec;16(6):518-23. doi: 10.1089/rej.2013.1530. PMID: 24199995.
6. Shokri-Kojori, E., Wang, G. J., Wiers, C. E., Demiral, S. B., Guo, M., Kim, S. W., Lindgren, E., Ramirez, V., Zehra, A., Freeman, C., Miller, G., Manza, P., Srivastava, T., De Santi, S., Tomasi, D., Benveniste, H., & Volkow, N. D. (2018). β-Amyloid accumulation in the human brain after one night of sleep deprivation. Proceedings of the National Academy of Sciences of the United States of America, 115(17), 4483–4488. https://doi.org/10.1073/pnas.1721694115
7. Barca-Mayo O, López M. Astrocyte Clocks and Glucose Homeostasis. Front Endocrinol (Lausanne). 2021 Mar 18;12:662017. doi: 10.3389/fendo.2021.662017. PMID: 33815298; PMCID: PMC8015704.