What is the Glymphatic System?

The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes

a unique system of perivascular channels, formed by astroglial cells, to promote efficient

elimination of soluble proteins and metabolites from the central nervous system of vertebrates.

What is the difference between the Lymphatic System and the Glymphatic System?

The lymphatic system clears soluble material, proteins and fluid from the interstitial space,

returning them to the general circulation. The lymphatic network extends throughout all parts of the

peripheral tissues and the density of lymph vessels correlates with the rate of tissue metabolism.

Although the brain and spinal cord are characterized by a disproportionately high metabolic rate,

the central nervous system does not have any conventional lymphatic vessels. The glymphatic

system clears waste from the brain and then connects to the lymphatic system which carries waste

products and destroyed bacteria back into the bloodstream. The liver or kidneys then remove these

from the blood and the body passes them out with other body waste, through bowel movements

and urine.

Why is it called “glymphatic”?

The name "glymphatic system" was coined by the Danish neuroscientist Maiken Nedergaard in

recognition of its dependence upon glial cells and the similarity of its functions to those of the

peripheral lymphatic system.

When was the Glymphatic System discovered or identified?

Neuroscientists at the University of Rochester Medical Center published their findings August 15,

2015. Maiken Nedergaard, M.D.,D.M.Sc, senior author of the paper said, “This work shows that the

brain is cleansing itself in a more organized way and on a much larger scale than has been

realized previously.”

How does the glymphatic system work?

Cerebrospinal fluid or CSF plays an important role in cleansing brain tissue, carrying away waste

products and carrying nutrients through brain tissue by a process known as diffusion. It works

slowly, more like a trickle. Because the glymphatic system internally creates its own pressure, it

circulates large volumes of CSF to every corner of the brain through what scientists call bulk flow

or convection.

How is the “pressure” created?

Glial cells, called astrocytes, use projections known as “end feet” to form a network of conduits

around the outsides of arteries and veins inside the brain. “End feet” are filled with structures

known as water channels or aquaporins, which move the CSF through the brain. The team found

that CSF is pumped into the brain along the channels that surround arteries, then washes through

brain tissue before collecting in channels around veins and draining from the brain into the

lymphatic system.

Why wasn’t this discovered earlier?

The system only operates in a living brain. Scientists were using dead brain tissue because

appropriate technology to view the flow of fluids inside a living brain, did not yet exist. The

discovery was made using two-photon microscopy, which allowed scientists to look at the flow of

blood, CSF and other substances in the brain of living mice, whose brains are very similar to the

human brain.

What makes this discovery so important for us?

As Jeffrey Iliff, PhD., a research assistant professor in the Nedergaard lab explained,

“Understanding how the brain copes with waste is critical. In every organ, waste clearance is as

basic an issue as how nutrients are delivered. In the brain, essentially all neurodegenerative

diseases, including Alzheimer’s disease, happen when protein waste accumulates and eventually

suffocates and kills the neuronal network of the brain. If the glymphatic system fails to cleanse the

brain as it is meant to, either as a consequence of normal aging, or in response to brain injury,

waste may begin to accumulate in the brain. Perhaps increasing the activity of the glymphatic

system might help prevent amyloid deposition from building up or could offer a new way to clean

out buildups of the material in established Alzheimer’s disease.”

Glymphatic fluid movement has the potential to alter local (within a brain region) as well as global

(brain-wide) transport of signaling molecules as well as metabolites known to be implicated in

homeostasis and specific behaviors. There is a potential for cross talk among the glymphatic

system, cardiovascular system, gastrointestinal tract, and the lymphatic system. Much remains to

be studied, but the Nedergaard team believe that the glymphatic/lymphatic system acts as a

cornerstone in the architecture of the brain and body signaling.

Is the Glymphatic System only a waste disposal system?

On the contrary, it is the place of transport of nutrients, including glucose, lipids, amino acids,

neurotransmitters, antigens, immune cells (as well as exchange of information via afferent and

efferent immune pathways) and fluid exchange. The efficient exchange of substances between the

cerebrospinal fluid and interstitial fluid allows the elimination of exogenous substances, albumins,

amyloid, dextrans (glucose polymers) from the interstitial spaces and removal of endogenously

produced proteins.

Another important function of the glymphatic system is immune surveillance of the central nervous

system. Glymphatic pathways allow the transport of antigens and immune cells and the exchange

of information via afferent and efferent immune routes. This is strongly impacted by the autonomic

nervous system, mostly the vagus nerve (research 1) (research 2).

Is the Glymphatic System working all the time?

The glymphatic system functions mainly during sleep; sleep and circadian timing both regulate

glymphatic function. During sleep, the brain enters a state of activity that enables elimination of

potentially neurotoxic waste products, including β-amyloid. We spend one third of our lives asleep,

without which we could not function. Sleep slows the metabolic rate so that increased attention and

energy can be given to repair and maintenance functions. Just as in sleep, the glymphatic system

is activated while a person is anesthetized during a medical procedure. Until the glymphatic system

was discovered, scientists were unaware that one extremely important function of sleep is to

reduce tissue resistance towards convective flow, facilitating interstitial spinal fluid and

cerebrospinal fluid exchange so that the brain can clear its waste metabolites, such as lactate,

peptides/proteins including amyloid-β and tau (a protein that helps stabilize the internal skeleton of

nerve cells (neurons) in the brain), along with a variety of contrast agents and tracers. (research)

Is there anything that could dysregulate the Glymphatic System?

Absolutely yes! Reduced sleep, jet lag, chronic stress, subarachnoid bleeding or stroke,

depression, head trauma, food deprivation, dehydration, poor body posture, drugs, disease and

aging can all lead to impairment or malfunction of the glymphatic system. Factors relating to

“aging” could be dehydration, lack of exercise, sedentary lifestyle, depression, lack of nutrient

foods, depolarization of astrocytes from the vascular “end feet”, incorrectly folded proteins and

protein build-up which can lead to inflammation and to an enlarged perivascular space, blocking

the clearance pathways.

How is the gut involved in the glymphatic system?

When discussing the gut–brain axis, it would be impossible not to mention the microbiome, which

is the host of bacteria present within the digestive tract that is essential not only for digestion, but

can also impact neuroendocrine and inflammatory responses in the gut. The microbiome has been

implicated in almost every disease of the nervous system, although the mechanisms of action are

relatively unclear (research). The vagus nerve provides a direct neural connection from the gut to

the brain. Upon feeding, the visceral branches of the vagus nerve are activated by a variety of

neuroendocrine cues. Vagus nerve stimulation leads to increased glymphatic influx (research).

Are there signs of a malfunctioning glymphatic system?

Some of the signs that your glymphatic system is “on the fritz” could be mood disorders, dementia,

sleep disturbance, sleep disorders. Much of the current research is looking at central nervous

system diseases/neurodegenerative diseases to see if and how they are related to the glymphatic

system. Scientists are studying Alzheimer’s disease, Parkinson’s disease, Huntington’s disease,

Amyotrophic lateral sclerosis (ALS), traumatic brain injury, stroke, idiopathic normal pressure

hydrocephalus and bipolar disorder. Although a lot more research needs to be done, current

studies tend to show that diseases of the central nervous system are in some way connected to a

malfunctioning glymphatic system.

How can we benefit from this information?

Given what current research is showing about the role and function of the glymphatic system, we

may be able to help ourselves to facilitate the optimal function of our own brain’s hard work to get

rid of anything that interferes with its homeostasis and good health. Eat “clean” food; drink filtered

water; get enough restful sleep; maintain good posture; do some kind of daily movement and find

reasons to laugh and be positive. These are the same things that affect our whole body’s health

and balance. You are worth the effort and your body will thank you.

To Schedule an assessment for BELD and/ or  Glymphatic System Drainage 

please call 416-924-8887 or email