The relationship between the lymphatic system and Alzheimer's disease wasdiscuss

Zi-Yi Zhang

The first clinical medical college, shaanxi university of Chinese medicine, Xianyang, China.

Abstract

Keywords:Tri-jiao theory, Glymphatic system, Alzheimer's disease ,Beta-amyloid

Background

The glymphatic system, also known as glial the glymphatic system, is a perivascular pathway in the whole brain.Depending on the characteristics of aquaporins in astrocytes, it can effectively remove soluble proteins and metabolic wastes produced by the central nervous system [1].The system was first found in mice and further demonstrated in animal and human experiments [2].In recent years, there are more and more studies on the glymphatic system.Some scholars pointed out that many central nervous system diseases, such as Alzheimer's disease (AD) and sleep disorders, are closely related to the dysfunctional operation of the central nervous system [3].Tri-jiao, as an important anatomical system in traditional Chinese medicine system, it can passe through waterways.Its function is to fight against external evils and remove harmful substances internally, thus shouldering the heavy responsibility of resisting external evils and removing harmful substances.The lymphatic system is the anatomical structure of modern medicine.There are similarities in structure and function between Tri-jiao and lymphatic system.The the glymphatic system is the part of the the lymphatic system in the brain, which is also the part of the Tri-jiao in the brain.Therefore,the theory of "Tri-jiao like glymphatic system" is put forward in order to provide new ideas for the treatment of AD by traditional Chinese medicine (TCM).

1 Tri-jiao theory

1.1 Name of Tri-jiao

Tri-jiao was first seen in "Inner Canon of the Yellow Emperor"[6]."It can be seen that "Inner Canon of the Yellow Emperor" classified it as one of the the six hollow organs, but did not describe its physiological and anatomical position, which is indeed a pity for later generations.What does Tri-jiao mean? Three, or refers to the upper, middle and lower three, or refers to the three yang.

1.2 Tri-jiao morphology

The concept of Tri-jiao began from "Inner Canon of the Yellow Emperor", which only describes its function but not its form, so the problem of visible and intangible arises.Due to the historical environment and the development of science, different generations of doctors hold different views, so there are still disputes.

1.2.1 Theory of name and invisibility

Those who think that it is well-known and invisible,such as "Nanjing" [5]:"there are only five viscera, and only the six hollow organs.Therefore, there are the six hollow organs, which is called tri-jiao.There is a difference between the primordial qi.It is famous but invisible to preside over all kinds of Qi." Later, Si-Miao Sun and other doctors also agreed with this theory.

1.2.2 Theory of name and visibility

Those who think that it is named and visible, such as He-Sheng Yao [4] thinks that the Tri-jiao should be a large omentum located in the chest and abdomen;He-bao Wang [6] thinks that the Tri-jiao is a variety of spaces in the human body, and its functions pass through all kinds of Qi and water;Yue Li [7] and others think that the Tri-jiao is the human lymphatic system.There are also some theories such as ion channel theory and circulation theory.In a word, due to the development of modern physiology and anatomy,doctors have more and more specific understanding of Tri-jiao, but they lack the specific demonstration of its function.

2 Correlation between tri-jiao, lymphatic system and Alzheimer's disease hypothesis

2.1 Correlation between tri-jiao, lymphatic system

Tri-jiao is the most similar to lymphatic system in physiological function and anatomical morphology.First of all, the tri-jiao is the end point of Qi and the starting point of Qi transformation.The one who is angry can resist external evils and delay aging.The lymphatic system is the important immune system of the human body, producing various immune cells.The Qi dissipating person can excrete toxic substances, and the lymphatic vessels are the main channels leading the lymph to remove the apoptotic cell debris and foreign bodies, connect with the venous vessels.The tri-jiao is consistent with the lymphatic system in function.Moreover,Inner Canon of the Yellow Emperorshows that there is material in and out of the tri-jiao.The lymphatic system is the main transport channel for the growth and immune substances of human body, and the tri-jiao system is the transportation channel for the fine substances and metabolites of water grains.They are independent and interact with each other.They are all powered by the beating of the heart.Therefore, it can be considered that the corresponding anatomical relationship between lymphatic system and tri-jiao is the most similar.

2.2 Glymphatic system -discovery of the distribution of tri-jiao in brain

The concept of glymphatic was proposed by Liff et al[8] in 2012.Dye was injected into the cerebrospinal fluid of the cerebellomedullary cistern of mice, and the transport of dye to the cerebral cortex of mice was observed.Result is that the dye initially appeared in the paravascular space of arterioles, then entered the brain parenchyma, and then entered the paravenous space.Its main function is to remove soluble protein and metabolic waste produced by central nervous system.The clearance pathway is that the choroid plexus produces cerebrospinal fluid, which flows into the space around the blood vessels under the joint action of arterial pulsation;respiration and cerebrospinal fluid pressure gradient, where it exchanges with the interstitial fluid and removes waste, and then crosses the surface of the brain accompanied by the arteries on the pia mater, descends into the brain along the perforating artery and enters the capillary bed [9].This experiment reveals several problems:(1) the existence of the glymphatic system;(2) the location of the glymphatic system is beside the artery and vein;(3)the function is to remove harmful substances from the brain;(4) the immune cells in the tissue fluid destroy the harmful substances in this space;(5) the remains of the inactivated substance were carried into the venous vessels by the perforating artery (lymphangioid) and finally discharged from the body.This is exactly the specific performance of the running water of tri-jiao,which leaves beneficial substances, inactivates and removes harmful substances.Therefore, the glymphatic system should belong to the category of tri-jiao.

2.3 Relationship between four types of the glymphatic system and Alzheimer's disease

AD is a neurodegenerative disease with cognitive impairment and memory impairment as its main clinical manifestations.Its important pathological feature is the deposition of senile plaques, and the main component of senile plaques is amyloid β (Aβ) [10].Aβ is the hydrolysate of amyloid precursor protein.There is an effective and balanced clearance mechanism in normal human brain, such as the glymphatic system,which can remove Aβ and other metabolic wastes.However, in AD patients, the clearance mechanism is unbalanced, resulting in increased accumulation and reduced excretion of metabolites.High aggregation of Aβ can induce neuronal apoptosis, cause neurotoxicity and damage the nervous system [11].The glymphatic system is a perivascular pathway in the whole brain.Aquaporin-4 on astrocytes is used to drive the rapid exchange and flow of cerebrospinal fluid and brain tissue fluid, which transports Aβ and other metabolites in brain tissue fluid from the periarterial space to the perivenous space, thus removing the brain [12].It is concluded that there is a close relationship between the clearance function of the glymphatic system and the progression of AD.With the development of aging,aquaporin-4 on astrocytes decreased and depolarized.Aquaporin-4 is the driving force of clearing and exchanging of the glymphatic system, The exchange rate of cerebrospinal fluid and brain tissue fluid and the clearance efficiency of Aβ were significantly decreased [1].In addition, reactive glial cells in the elderly can increase the depolarization of heavy water channel protein 4, thus reducing the Aβ and other products of the glymphatic system clearance [13].Genetic, cardiovascular and cerebrovascular diseases can easily lead to the occurrence or aggravation of AD.It can be seen that with the increase of age, the function of the glymphatic system decreases actively,which can accelerate the production or progress of AD[14].In addition, Aβ deposition can lead to abnormal distribution of aquaporin-4 and slow down the fluid flow rate of the system [2].It can be seen that a large amount of Aβ protein deposits in AD patients, resulting in passive decline of the glymphatic system function,thus affecting the normal operation of the system.The glymphatic system is closely related to AD and has important clinical value.The diagnosis and treatment of AD by maintaining the normal function of the glymphatic system can be regarded as a new direction of diagnosis and treatment.

2.4 Treatment in Alzheimer's disease through trijiao

AD belongs to the category of "Dai Bing" in TCM.It is mainly manifested in memory and cognitive impairment, decline in life ability, abnormal mental behavior, and serious decline in quality of life [15].The disease is located in the brain, and the main causes are senile asthenia, chronic disease and internal injury,which lead to a great loss of healthy qi in human body.Stagnation of qi, phlegm and blood stasis in the body.The abatement of collaterals and brain marrow and mental apraxia develop into dementia[16].The disease is related to deficiency, fire, phlegm and blood stasis.In the tri-jiao, the Qi can't rise and the vitality is weak.The function of dividing the brain of the tri-jiao decreases, and the function of fighting against external evils.The toxin deposits in the brain and affects the conscious activity.The clinical manifestations include memory disorder, empty speech, loss of ideation and spatial cognition.The symptoms of tri-jiao include restlessness, increased speech, forgetfulness, high emotion and ignorance of hunger.Phlegm can not only blind the mind, but also attack the brain, block the brain collaterals, resulting in the loss of mental function.Clinical manifestations include depression, poor appetite, mental depression, memory loss, dizziness and so on.If the tri-jiao is blocked, Qi stagnation and blood stasis will occur.If the tri-jiao is blocked, Qi stagnation and blood stasis will appear in the brain along with the meridians.In light, it will blind the mind and lead to loss of ideation and spatial cognition, which is manifested as forgetfulness and slow reaction.In severe cases, blood stasis will block the brain collaterals and cause blood vessel rupture, which can lead to cerebral hemorrhage and death.

Discussion

Through the analysis of the correlation among tri-jiao,the glymphatic system and AD, there are new research and inspiration for the diagnosis and treatment of AD.Clinical methods can be used to improve the quality of life of patients with AD, such as dredging tri-jiao,filling with fire, promoting the metabolic clearance of amyloid beta protein in the glymphatic system.

In the aspect of traditional medicine, Liang-Duo Jiang[17] thinks that tri-jiao obstruction is a group of clinical symptoms characterized by "upper heat and lower cold, internal heat and external cooling, disharmony of dryness and dampness, and obstruction of left and right".The main prescription is Chaigui decoction.It is believed that Chaigui decoction can dredge Qi regulating mechanism, drive away external evils in a way of promoting Qi penetration.Yong-Kang Zhang[18] thinks that Xiaochaihu decoction has the function of reconciling Shaoyang and regulating the cardinal.It can open the exterior and interior axis of the gallbladder meridian of Shaoyang, and the tri-jiao can be unblocked, the liver and gallbladder can be regulated,and the spleen and stomach can be transported.Jun-Mei Chen et al [19] pointed out that Lingguizhugan decoction has been proved to significantly inhibit and eliminate the deposition of amyloid beta protein,affect the clearance pathway of the glymphatic system, improve the brain microenvironment, so as to improve dementia.Acupuncture treatment is now very extensive.Acupuncture at relevant points on the head can regulate the drainage of the glymphatic system, promote the excretion of metabolic wastes in the brain, and thus slow down the formation of AD.Modern medical research suggests that increasing vascular pulsation can accelerate the clearance of amyloid beta protein in the brain, thus preventing AD[20].Estrogen has the effect of protecting and repairing neurons.Estrogen can reduce the toxic damage of amyloid beta protein to nerve, and promote the decomposition of amyloid beta protein [21].Now the incidence rate of AD is increasing.It has become one of the most common neurodegenerative diseases and has attracted much attention.Both traditional medicine and modern medicine have profound research and understanding on the causes and clinical treatment of the disease.Through the understanding of the theory of "glymphatic system tri-jiao", we can provide more extensive ideas for the treatment of AD, and combine traditional Chinese and western medicine in clinical treatment.Of course, the reason is still deep, and we need further research and study.