Acknowledgements
Page: iii-iii (1)
Author: Gaiqing Wang
DOI: 10.2174/9789815313086124010003
Introduction
Page: iv-v (2)
Author: Gaiqing Wang
DOI: 10.2174/9789815313086124010004
Entrance of Exotic Pathogens into the Brain
Page: 1-8 (8)
Author: Gaiqing Wang, Haiyun Chen*, Juan Yang, Jing Wang, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010005
Abstract
CNS infections are life-threatening diseases caused by viral, bacterial, parasitic, and fungal microorganisms, including meningitis, encephalitis, and brain abscess. These infections are linked to significant illnesses and death rates. CNS is characterized by a specific structure and function. Despite a unique system of brain barriers and an autonomous immune system, CNS is very susceptible to microorganisms, which may invade directly via the BBB, blood, or less frequently by reverse axonal transport.
Deposition of Abnormal Proteins in the Brain
Page: 9-28 (20)
Author: Gaiqing Wang*, Haiyun Chen, Juan Yang, Jing Wang, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010006
Abstract
A common feature of neurodegenerative diseases is the abnormal accumulation of misfolded proteins in the brain, such as amyloid beta (Aβ), tau, αsynuclein, fused in sarcoma (FUS), and TAR DNA-binding protein 43 (TDP-43), which lead to selective neuronal degeneration and dysfunction. Dysfunction in the removal of these misfolded proteins from the brain, which is thought to be a major cause of neurodegenerative diseases and a major therapeutic target for their cure.
Harmful Effects of Metal Deposits in the Brain
Page: 29-43 (15)
Author: Gaiqing Wang*, Haiyun Chen, Juan Yang, Jing Wang, Bo Yan, Minglei Chen and Shaoping Wu
DOI: 10.2174/9789815313086124010007
Abstract
Metal deposits in the brain can lead to various harmful effects, which can
depend on factors such as the type of metal, its amount and location of deposition, and
the individual's overall health. These effects may include:
1. Neurotoxicity: Metals like lead, mercury, and arsenic can directly damage neurons
and interfere with their normal functioning, leading to neurological symptoms and
cognitive impairments.
2. Inflammation: Metal deposits can trigger an inflammatory response in the brain,
leading to tissue damage and exacerbating neurodegenerative processes.
3. Oxidative stress: Metals can induce oxidative stress, causing an imbalance between
free radicals and antioxidants in brain cells, which can lead to cellular damage and
dysfunction.
4. Impaired neurotransmitter function: Metals can disrupt neurotransmitter systems in
the brain, affecting communication between neurons and leading to cognitive and
behavioral changes.
5. Compromised blood-brain barrier: Some metals can weaken the blood-brain barrier,
allowing harmful substances to enter the brain more easily and exacerbating neuronal
damage.
6. Increased risk of neurodegenerative diseases: Metal deposition has been linked to an
increased risk of neurodegenerative diseases such as Alzheimer's disease, Parkinson's
disease, and amyotrophic lateral sclerosis (ALS).
7. Cellular dysfunction: Metals can interfere with cellular processes and signaling
pathways, leading to cellular dysfunction and contributing to neurological disorders.
It is crucial to minimize exposure to toxic metals through proper safety measures and
environmental regulations. If metal deposition in the brain is suspected or confirmed,
seeking medical attention is important to evaluate the extent of damage and determine
appropriate treatment strategies to mitigate harmful effects.
Response to Foreign Pathogens in the Brain
Page: 44-47 (4)
Author: Gaiqing Wang, Haiyun Chen*, Juan Yang, Jing Wang, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010008
Abstract
The brain's defense against foreign invaders involves a specialized immune system called the neuroimmune system. It includes microglia, astrocytes, and other immune cells. Microglia detect and respond to abnormalities, while astrocytes help maintain the blood-brain barrier and participate in immune signaling. Together, these cells protect the brain from pathogens and maintain its health. Understanding the neuroimmune system is crucial for combating brain infections and inflammatory disorders.
Reaction to Abnormal Protein Precipitation in the Brain
Page: 48-62 (15)
Author: Gaiqing Wang, Haiyun Chen*, Juan Yang, Jing Wang, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010009
Abstract
The response to abnormal protein deposits in the brain involves a complex interaction among various components of the immune system. Initially, the immune response aims to clear the protein aggregates. However, in neurodegenerative diseases, chronic inflammation and immune dysregulation can occur, leading to additional damage.
Reaction to Abnormal Metal Accumulation in the Brain
Page: 63-66 (4)
Author: Gaiqing Wang, Haiyun Chen, Juan Yang, Jing Wang*, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010010
Abstract
The immune response to metal deposits in the brain can vary depending on the type of metal and specific circumstances. Generally, the immune system identifies metal deposits as antigens and triggers immune cells to eliminate them.
The Function of Neurovascular Unit in Clearance System
Page: 67-79 (13)
Author: Gaiqing Wang, Haiyun Chen, Juan Yang, Jing Wang, Bo Yan* and Minglei Chen
DOI: 10.2174/9789815313086124010011
Abstract
The neurovascular unit (NVU) encompasses multiple cellular elements such as the BBB, astrocytes, microglia, and pericytes. Together, these components form a system that aids in the removal of waste products, toxins, and surplus neurotransmitters from the brain tissue. The NVU's functions include circulatory regulation, perivascular drainage, and phagocytic degradation clearance systems. Its pivotal role lies in preserving brain homeostasis and thwarting the buildup of detrimental substances that might otherwise impede regular brain function.
Phagocytosis and Scavenger Receptors in the Brain
Page: 80-89 (10)
Author: Gaiqing Wang*, Haiyun Chen, Juan Yang, Jing Wang, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010012
Abstract
Phagocytosis is a vital process where immune cells called phagocytes engulf and digest foreign particles, pathogens, and cellular debris. This process is crucial for tissue homeostasis and infection defense. Scavenger receptors, found on immune cells like microglia, recognize and bind to diverse ligands such as pathogens, altered self-molecules, and cellular debris. They are pivotal in facilitating phagocytosis and clearing these substances from the body.
The Role of Cerebrospinal Fluid in the Clearance System
Page: 90-93 (4)
Author: Gaiqing Wang*, Haiyun Chen, Juan Yan, Jing Wang, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010013
Abstract
The cerebrospinal fluid (CSF) system is vital for maintaining the brain's environment and clearing waste. The BBB-CSF barriers regulate the movement of molecules between the blood and brain fluids. CSF flow is driven by arterial pulsation and may be influenced by vascular muscle. The glymphatic system helps drain interstitial fluid, especially during sleep. Anesthesia may impair CSF circulation, affecting brain waste clearance. Meningeal lymphatic vessels also assist in CSF clearance and immune cell movement. Understanding these processes can lead to new treatments for neurological disorders.
The Role of Brain Vasculature and the Perivascular Space
Page: 94-97 (4)
Author: Gaiqing Wang, Haiyun Chen, Juan Yang, Jing Wang, Bo Yan and Minglei Chen*
DOI: 10.2174/9789815313086124010014
Abstract
The brain vasculature encompasses a network of blood vessels responsible for supplying oxygen and nutrients and eliminating waste from the brain. This network includes arteries, veins, and capillaries. The perivascular space is a fluid-filled region surrounding these blood vessels within the brain, situated between the vessel walls and the brain tissue. Functioning as part of the glymphatic system, the perivascular space serves as a pathway for clearing waste products from the brain by facilitating their transport along the blood vessels and subsequent drainage out of the brain.
The Role of the Glymphatic System
Page: 98-106 (9)
Author: Gaiqing Wang, Haiyun Chen, Juan Yang, Jing Wang, Bo Yan and Minglei Chen*
DOI: 10.2174/9789815313086124010015
Abstract
The glymphatic system, a recently identified waste clearance pathway in the brain, is crucial for removing waste products and maintaining brain homeostasis. Similar to the lymphatic system in the body, the glymphatic system operates uniquely within the brain. Its main role is to clear various waste products, such as metabolites, proteins, and toxins, from the brain. AQP4 plays a pivotal role in facilitating the function of this system.
The Role of Meningeal Lymphatic Systems
Page: 107-112 (6)
Author: Gaiqing Wang, Haiyun Chen, Juan Yang, Jing Wang, Bo Yan and Minglei Chen*
DOI: 10.2174/9789815313086124010016
Abstract
The meningeal lymphatic system is a newly identified network of lymphatic vessels located within the meninges, the protective membranes enveloping the brain and spinal cord. This system is essential for clearing waste products, supporting immune responses, and ensuring the balance of brain functions.
The Target Therapeutic Approach for the BBB
Page: 113-120 (8)
Author: Gaiqing Wang, Haiyun Chen, Juan Yang*, Jing Wang, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010017
Abstract
The blood-brain barrier (BBB) is crucial for maintaining the microenvironment needed for proper neuronal function. BBB breakdown can lead to immune cell infiltration and uncontrolled movement of molecules and ions, contributing to neurodegenerative diseases. Repairing the BBB is a key therapeutic strategy for treating neurological disorders, utilizing methods such as glucocorticosteroids (GCs) and mesenchymal stromal cells (MSCs). GCs can restore BBB integrity by regulating tight junction proteins (TJs), while MSCs show potential in promoting angiogenesis and BBB repair. Although these strategies are promising, further research is needed to determine their safety and effectiveness for clinical use.
The Regulatory Mechanism Targeting Microglia
Page: 121-133 (13)
Author: Gaiqing Wang, Haiyun Chen, Juan Yang*, Jing Wang, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010018
Abstract
Microglia are vital immune cells in the central nervous system (CNS) responsible for maintaining brain balance and responding to injuries or infections. They are regulated by a variety of mechanisms involving interactions with different signaling molecules and cell types within the CNS. Ensuring proper regulation of microglial activity is essential for preserving brain health and preventing the onset of neuroinflammatory and neurodegenerative disorders.
The Regulatory Mechanism for Astrocyte Polarization
Page: 134-150 (17)
Author: Gaiqing Wang*, Haiyun Chen, Juan Yang, Jing Wang, Bo Yan, Minglei Chen and Chuntian Liang
DOI: 10.2174/9789815313086124010019
Abstract
Astrocyte polarization is a multifaceted process governed by various mechanisms such as developmental and environmental cues, transcription factors, signaling pathways, epigenetic modifications, and interactions with other cells. Gaining insights into these regulatory mechanisms is vital for unraveling the significance of astrocytes in brain development and overall brain function.
The Regulatory Mechanism for Scavenging Pathways
Page: 151-154 (4)
Author: Gaiqing Wang*, Haiyun Chen, Juan Yang, Jing Wang, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010020
Abstract
Scavenging pathways are essential for cells to recycle and reuse cellular
components. These pathways are regulated by a complex network of mechanisms that
ensure efficient scavenging and recycling of cellular materials. The regulatory
mechanisms involved are intricate and interconnected, employing multiple levels of
control to facilitate the proper recycling and reuse of cellular components.
In our previous discussions, we outlined the upstream regulatory mechanisms and
intervention strategies for scavenger receptors following ICH [44].
The Regulatory Mechanism for Glymphatic System
Page: 155-181 (27)
Author: Gaiqing Wang*, Haiyun Chen, Juan Yang, Jing Wang, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010021
Abstract
The regulatory mechanism of the glymphatic system is a complex interplay involving multiple factors and processes. These include CSF production, arterial pulsations, astrocytic water channels (AQP4), the sleep-wake cycle, AQP4 polarization, and BBB permeability. Together, these factors ensure the efficient clearance of waste products from the brain, contributing to overall brain health.
Effect Factors of Meningeal Lymphatics (MLVs)
Page: 182-188 (7)
Author: Gaiqing Wang*, Haiyun Chen, Juan Yang, Jing Wang, Bo Yan and Minglei Chen
DOI: 10.2174/9789815313086124010022
Abstract
The regulatory mechanism for meningeal lymphatics is not fully understood
yet, but research is ongoing to uncover its functions and regulation. Several factors play
a role in regulating these vessels, including:
Circadian Rhythm: There is evidence suggesting that MLVs exhibit circadian rhythms
in their function. For example, studies have shown variations in the clearance of waste
molecules from the brain via MLVs based on circadian rhythms.
CSF Flow: The flow of CSF is intricately connected with MLVs' function. Changes in
CSF dynamics, such as pressure or flow rate, can influence the activity and
permeability of MLVs.
Astrocytes: Astrocytes, a type of glial cell in the brain, have been implicated in the
regulation of MLVs. They are known to play roles in maintaining brain homeostasis
and responding to changes in the brain microenvironment, which can affect MLV
function.
Signaling Molecules: Various signaling molecules, including cytokines, growth factors,
and chemokines, are involved in the regulation of MLVs. These molecules can
modulate the permeability, inflammation, and immune responses associated with
MLVs.
Immune Cells: Immune cells, such as macrophages and lymphocytes, interact with
MLVs and contribute to their regulation. These cells can influence the inflammatory
status and immune surveillance within the meninges, affecting MLV function.
Understanding the complex interplay among these factors is crucial for unraveling the
regulatory mechanisms of MLVs and their significance in brain health and disease.
Ongoing research aims to elucidate these mechanisms further and explore potential
therapeutic targets related to MLVs in conditions like neuroinflammation,
neurodegenerative diseases, and brain injuries.Circadian rhythm, CSF, Meningeal lymphatics vessels (MLVs),
Regulation, Signaling molecules.
References
Page: 189-194 (6)
Author: Gaiqing Wang
DOI: 10.2174/9789815313086124010023
List of Abbreviations
Page: 195-200 (6)
Author: Gaiqing Wang
DOI: 10.2174/9789815313086124010024
Subject Index
Page: 201-206 (6)
Author: Gaiqing Wang
DOI: 10.2174/9789815313086124010025
Introduction
Waste Clearance in the Brain provides an in-depth exploration of the brain`s essential waste clearance systems, focusing on the glymphatic and cerebrospinal fluid pathways. This book examines the body`s natural defense mechanisms against harmful substances like abnormal proteins and metal deposits linked to neurodegenerative diseases such as Alzheimer`s. With clear explanations, it covers how foreign pathogens and harmful proteins are managed by cerebrospinal fluid, brain vasculature, and the meningeal lymphatic systems. It also discusses cutting-edge research on therapeutic approaches targeting the blood-brain barrier and brain cell regulation. Key Features: - Comprehensive overview of brain waste clearance pathways and systems - Examination of abnormal protein and metal deposition impacts on brain health - Insights into potential therapies for neurodegenerative diseases - Discussion on the brain`s vascular and immune system roles in waste clearance