Glymphatic system: what it is and what functions it performs in the human body

The lymphatic system, also known as the lymphoid system, is made up of a network of vessels, nodes and organs that are part of the immune system. The lymphatic vessels carry a clear fluid called lymph back to the heart for recirculation.

The main purpose of the lymph is immunological defense; removes foreign bacteria and other agents from the body. Lymph contains waste products, proteins, antibodies, and dead cells, as well as microbes. Lymphoid organs are made up of lymphoid tissue and are the sites of production and activation of various immune cells.

Until recently, the brain and spinal cord were thought to lack a lymphatic system. However, the existence of a kind of cerebral lymphatic system has recently been demonstrated. This macroscopic waste disposal system is called the glymphatic system because of its dependence on glial cells and its functions homologous to those of the lymphatic system within the central nervous system.

In this article we explore the glymphatic system, its main functions and the implications for the treatment of neurodegenerative diseases of this discovery.

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What is the glymphatic system?

The glymphatic system is a network of vessels used to remove waste from the central nervous system or CNS. This system is especially active while we sleep, it eliminates toxins and other waste from brain metabolism. Recently, research has shown that the glymphatic system can become disrupted and function less over time; this has been suggested as a possible cause of some neurodegenerative diseases.

The glymphatic system is the cerebral and spinal counterpart of the lymphatic system. The lymphatic system supports the immune system and provides a pathway parallel to the circulatory system for the removal of fluids from the body. This system transports excess interstitial fluids, proteins, and waste materials out of the various organs and body tissues. These substances are discarded to regulate fluid volume and osmotic pressure; this is critical because failure to remove these soluble proteins can cause serious blockages.

Any blockage in the lymphatic ducts can have dramatic consequences. In cases of elephantiasis, a disease caused by lymphatic parasites, chronic edema occurs when lymph clearance stops and interstitial solutes accumulate.

Paradoxically, the lymphatic system does not extend to the central nervous system: the brain and spinal cord. Until the discovery of the gingláfatico system, several hypotheses were raised about how the brain eliminated waste.

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brain cleaning model

The brain, like all organs of our body, produces metabolic waste, all enzymatic reactions produce waste that must be eliminated. The glymphatic system is made up of water channels and uses cerebrospinal fluid as a transport fluid.

The cerebrospinal fluid (CSF) is a clear, colorless fluid that surrounds the brain and spinal cord. Its main function is protection: it helps cushion blows or injuries. Also is responsible for removing waste products from the nervous system. However, the manner in which the various residues were exchanged between brain tissue and cerebrospinal fluid is a recent discovery.

A 2012 study led by M. Nedergaard and researchers at the University of Rochester used two-photon fluorescence imaging to look at the arachnoid cerebrospinal fluid of live mice. Through in vivo two-photon excitation microscopy, the Rochester team was able to observe cerebrospinal fluid flow in real time without having to drill into the compartment.

According to their findings, cerebrospinal fluid is exchanged with the interstitial fluid surrounding the brain through the paravascular spaces that surround the great veins and facilitate drainage.

Normally, the cerebrospinal fluid is separated from the brain tissue, preventing the exchange of substances. However, the traditional model of cerebrospinal fluid hydrodynamics has been firmly challenged. We now know that cerebrospinal fluid is able to enter the spaces next to the smallest blood vessels that reach the brain (the spaces of Virchow). There, it can be exchanged with interstitial fluid; This happens thanks to a channel formed by the astrocytes. The feet of these glial cells surround the space that surrounds the capillaries of the brain, forming the glymphatic channels. Where does the interstitial fluid of the brain circulate?

The exchange of materials via glymphatic transport results from still partly unknown energy sources. Mainly, the energy is obtained from the pulsations of the arteries and the pressure created by making the cerebrospinal fluid. Waste products such as proteins and metabolites are removed from the brain tissue and transported to the cerebrospinal fluid for disposal. Approximately 50% of the cerebrospinal fluid reaches the cervical lymph nodes for filtration.

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What influences the functioning of the glymphatic system?

The ability of the lymphatic system to function properly depends on several physiological aspects of different organs of our body. These include the immune system, the heart system, and the circulatory system. Lifestyle, disease, and inflammation can all have negative effects on the glymphatic system. These alterations can cause glymphatic drainage to be slower., negatively affecting the health of the body in general and mainly the brain.

Studies have shown that the lymphatic system is more efficient and robust when the heart is pumping, the blood is flowing, the body is relaxed, and the brain is enjoying restful sleep.

The brain performs housekeeping functions during sleep. This is because the glymphatic system is more active at that time. Exchange between cerebrospinal fluid and interstitial fluid is more efficient due to increased extracellular space.

Different studies have shown that it expands by 60% during sleep. Based on these findings, it is believed that increased glymphatic clearance during the night could be one of the causes of the restorative properties of sleep.

The aging process affects glymphatic transport, specifically the channel expressed by astrocytes that performs most of the system's exchange. The canal can also deteriorate due to sleep deprivation. Some studies have shown that exercise can mitigate these effects in mice. This suggests that physical activity could have a neuroprotective function.

Relationship of the glymphatic system and neurodegenerative diseases

Some neurodegenerative diseases may be caused by age-related changes in glymphatic function. These include alterations in the glial cells responsible for creating the glymphatic vessels, decreased production of cerebrospinal fluid by the choroid plexuses the reduction of flexibility and arterial pulsations that provide the necessary energy to the exchange with interstitial fluid, and decreased ability of CSF to move through the brain.

The glymphatic system removes large proteins from the brain during sleep. One of those proteins is amyloid beta, which is the main component of the brain plaques associated with Alzheimer's disease. Impairment of the glymphatic system may also be involved in stroke and cortical spreading depression.

The researchers believe that increased glymphatic transport could potentially delay the onset of Alzheimer's disease and other neurodegenerative diseases. Animal experiments show that reduced glymphatic transport often precedes disease; therefore, they would allow us to conclude that greater glymphatic transport could help postpone the onset of the disease.

The relationship between glymphatic function and exercise opens up a possibility of new treatments for neurodegenerative diseases. These treatments are likely to be more effective if given early in the progression of dementia. Methods to assess glymphatic flow through magnetic resonance imaging or positive emission tomography are currently being developed as clinical diagnostic tools.

The glymphatic system may have more functions than waste removal. In the future, it could also be involved in the delivery of growth factors and drugs, research suggests.