Many of us are relatively familiar with the lymphatic system; it performs a number of roles, one of which is clearing metabolic waste from the gaps between cells, referred to as the interstitial space.
However, the central nervous system (CNS), which comprises the brain and spinal cord, does not have any true lymphatic vessels.
Because the CNS is highly active, metabolic waste can build up quickly.
The CNS is also very sensitive to fluctuations in its environment, so the body needs to remove cellular garbage somehow, and that’s where the glymphatic system comes in.
Before the discovery of this brain-based garbage disposal system, scientists believed that each individual cell handled its own metabolic detritus.
If the cellular system became overloaded or slowed down as we aged, metabolic garbage would build up between the cells. This garbage includes products such as beta-amyloid — the protein associated with Alzheimer’s disease.
Astroglia
The term “glymphatic” was coined by Maiken Nedergaard, a Danish neuroscientist who discoveredthe system. The name is a reference to the glial cells, which are vital to this waste clearance system.
Glial cells get relatively little coverage, compared with neurons, despite being just as numerous in the brain. They were long considered little more than lowly support cells, but are now held in higher regard.
Glia protect, nourish, and insulate neurons. They also play a role in the immune system and, as we now know, the glymphatic system.
In particular, a type of glial cell known as astroglia are important. Receptors, called aquaporin-4 channels, on these cells allow cerebrospinal fluid (CSF) to move into the CNS, setting up a current that shunts fluid through the system.
CSF is a clear fluid that surrounds the CNS, providing it with mechanical and immunological protection, among other things.
The glymphatic system, which runs parallel to arteries, also harnesses the pulsing of blood in circulation to help keep things moving.
As the blood vessels expand rhythmically, they drive the exchange of compounds between the interstitial space and the CSF.
The glymphatic system connects with the lymphatic system of the rest of the body at the dura, a thick membrane of connective tissue that covers the CNS.
The importance of sleep
Following Nedergaard’s discovery, she ran a series of experiments on mice to develop a better understanding of how this system worked and when it was most active. In particular, the team focused on sleep and Alzheimer’s.
Nedergaard and her team found that the glymphatic system was most busy as the animals slept. They showed that the volume of interstitial space increased by 60% while the mice were sleeping.
This volume increase also boosted the exchange of CSF and interstitial fluid, speeding up the removal of amyloid. They concluded that:
This early work inspired a wave of new studies, the most recent of which was published this month. The researchers looked at the impact of high blood pressure on the function of the glymphatic system.
Over time, high blood pressure causes blood vessels to lose their elasticity, becoming increasingly stiff. Because the regular pulsing of arterial walls drives the glymphatic system, this stiffening impedes its function.
Using a mouse model of hypertension, the scientists demonstrated that high blood pressure-induced artery stiffening did interfere with the way that the garbage disposal system worked; it prevented it from efficiently getting rid of large molecules in the brain, such as beta-amyloid.
This finding might help explain why scientists have found links between elevated blood pressureand cognitive decline and dementia.
Parkinson’s disease
Parkinson’s disease is another condition characterized by the buildup of protein in the brain. In this case, the protein is alpha-synuclein.
This has led some researchers to wonder whether the glymphatic system might be implicated here, too.
In Parkinson’s disease, there is disruption in the dopamine pathways of the brain. These pathways play an important role in sleep-wake cycles and circadian rhythms; therefore, people with Parkinson’s often experience sleep disturbances.
A review published in Neuroscience & Biobehavioral Reviews proposes that the disrupted sleep patterns could hinder the glymphatic removal of debris, including alpha-synuclein, helping it build up in the brain.
Brain trauma
Chronic traumatic encephalopathy results from repeated blows to the head; it used to be called “punch-drunk” syndrome because it occurs in boxers.
Symptoms can include memory loss, mood changes, confusion, and cognitive decline.
Some researchers believe that disruptions to the glymphatic system caused by brain trauma may increase the risk of developing chronic traumatic encephalopathy.
The authors of the review write that, following a traumatic brain injury, “Difficulties with sleep onset and maintenance are among the most commonly reported symptoms.”
As we have seen, this interferes with the glymphatic clearance of proteins from the interstitial space during sleep.