-
Trends in Neurosciences Jul 2020The glymphatic concept along with the discovery of meningeal lymphatic vessels have, in recent years, highlighted that fluid is directionally transported within the... (Review)
Review
The glymphatic concept along with the discovery of meningeal lymphatic vessels have, in recent years, highlighted that fluid is directionally transported within the central nervous system (CNS). Imaging studies, as well as manipulations of fluid transport, point to a key role of the glymphatic-lymphatic system in clearance of amyloid-β and other proteins. As such, the glymphatic-lymphatic system represents a new target in combating neurodegenerative diseases. Not unexpectedly, introduction of a new plumbing system in the brain has stirred controversies. This opinion article will highlight what we know about the brain's fluid transport systems, where experimental data are lacking, and what is still debated.
Topics: Brain; Central Nervous System; Glymphatic System; Humans; Lymphatic Vessels; Neurodegenerative Diseases
PubMed: 32423764
DOI: 10.1016/j.tins.2020.04.003 -
Wounds : a Compendium of Clinical... Mar 2020The lymphatic system is arguably the most neglected bodily system. As a result, its contribution to human health and disease is not well understood. In this review, the... (Review)
Review
The lymphatic system is arguably the most neglected bodily system. As a result, its contribution to human health and disease is not well understood. In this review, the clinical approaches based on new knowledge and developments of the lymphatic system are covered. The lymphatic system has 3 major functions: (1) the preservation of fluid balance; (2) a nutritional function, as intestinal lymphatics are responsible for fat absorption; and (3) host defense. Lymph vessels return the capillary ultrafiltrate and escaped plasma proteins from most tissues back, ultimately, to the blood circulation. Hence, lymphatics are responsible for maintaining tissue (and plasma) volume homeostasis. Impaired lymph drainage results in peripheral edema (lymphedema) and may have more far-reaching effects on cardiovascular disease, in particular hypertension and atherosclerosis. Lymphatics have an important immune surveillance function, as they represent the principal route of transport from tissues for antigen and immune cells. Intestinal lymphatics (lacteals) are responsible for most fat absorption, first documented by Gaspare Aselli in 1627, when the lymphatic system was discovered. A relationship between fat and lymphatics may exist well beyond the gut alone. Fat deposition is a defining clinical characteristic of lymphedema. Suction-assisted lipectomy of lymphedema has shown the swelling is not just fluid but is dominated by fat. Lymphatics are the preferred route for the metastatic spread of cancer. Accordingly, the lymphatic system may be important for defense against cancer by generating immune responses to malignant cell antigens. Preventing lymphatic entry and propagation of malignant metastasis would effectively render the cancer nonfatal. As one can see, the lymphatic circulation is fundamentally important to cardiovascular disease, infection and immunity, cancer, and, in all likelihood, obesity - 4 of the major challenges to health care in the 21st century.
Topics: Humans; Lymphatic System; Lymphedema; Lymphoscintigraphy
PubMed: 32163039
DOI: No ID Found -
Comprehensive Physiology Dec 2018The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic... (Review)
Review
The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic environment for every cell in all tissues of the body. The lymphatic system maintains extracellular fluid homeostasis favorable for optimal tissue function, removing substances that arise due to metabolism or cell death, and optimizing immunity against bacteria, viruses, parasites, and other antigens. This article provides a comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease. © 2019 American Physiological Society. Compr Physiol 9:207-299, 2019.
Topics: Animals; Homeostasis; Humans; Lymphatic System
PubMed: 30549020
DOI: 10.1002/cphy.c180015 -
The Journal of Clinical Investigation Sep 2017Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we... (Review)
Review
Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Central Nervous System; Central Nervous System Diseases; Dura Mater; Extracellular Fluid; Humans; Immune System; Lymph Nodes; Lymphatic System; Lymphatic Vessels; Meninges; Neuroglia
PubMed: 28862640
DOI: 10.1172/JCI90603 -
The Journal of Experimental Medicine Jun 2015The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes...
The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.
Topics: Analysis of Variance; Animals; Brain; Cerebrospinal Fluid; Extracellular Fluid; Fluorescent Antibody Technique; Galactosides; Green Fluorescent Proteins; Image Processing, Computer-Assisted; Indoles; Lymph Nodes; Lymphatic System; Macromolecular Substances; Mice; Mice, Transgenic; Microscopy, Confocal
PubMed: 26077718
DOI: 10.1084/jem.20142290 -
Biomolecules May 2022There is a growing prevalence of vascular cognitive impairment (VCI) worldwide, and most research has suggested that cerebral small vessel disease (CSVD) is the main... (Review)
Review
There is a growing prevalence of vascular cognitive impairment (VCI) worldwide, and most research has suggested that cerebral small vessel disease (CSVD) is the main contributor to VCI. Several potential physiopathologic mechanisms have been proven to be involved in the process of CSVD, such as blood-brain barrier damage, small vessels stiffening, venous collagenosis, cerebral blood flow reduction, white matter rarefaction, chronic ischaemia, neuroinflammation, myelin damage, and subsequent neurodegeneration. However, there still is a limited overall understanding of the sequence and the relative importance of these mechanisms. The glymphatic system (GS) and meningeal lymphatic vessels (mLVs) are the analogs of the lymphatic system in the central nervous system (CNS). As such, these systems play critical roles in regulating cerebrospinal fluid (CSF) and interstitial fluid (ISF) transport, waste clearance, and, potentially, neuroinflammation. Accumulating evidence has suggested that the glymphatic and meningeal lymphatic vessels played vital roles in animal models of CSVD and patients with CSVD. Given the complexity of CSVD, it was significant to understand the underlying interaction between glymphatic and meningeal lymphatic transport with CSVD. Here, we provide a novel framework based on new advances in main four aspects, including vascular risk factors, potential mechanisms, clinical subtypes, and cognition, which aims to explain how the glymphatic system and meningeal lymphatic vessels contribute to the progression of CSVD and proposes a comprehensive insight into the novel therapeutic strategy of CSVD.
Topics: Animals; Brain; Central Nervous System; Cerebral Small Vessel Diseases; Glymphatic System; Humans; Lymphatic System; Meninges
PubMed: 35740873
DOI: 10.3390/biom12060748 -
Molecular Neurodegeneration Aug 2023Alzheimer's disease (AD) is an aging-related form of dementia associated with the accumulation of pathological aggregates of amyloid beta and neurofibrillary tangles in... (Review)
Review
Alzheimer's disease (AD) is an aging-related form of dementia associated with the accumulation of pathological aggregates of amyloid beta and neurofibrillary tangles in the brain. These phenomena are accompanied by exacerbated inflammation and marked neuronal loss, which altogether contribute to accelerated cognitive decline. The multifactorial nature of AD, allied to our still limited knowledge of its etiology and pathophysiology, have lessened our capacity to develop effective treatments for AD patients. Over the last few decades, genome wide association studies and biomarker development, alongside mechanistic experiments involving animal models, have identified different immune components that play key roles in the modulation of brain pathology in AD, affecting its progression and severity. As we will relay in this review, much of the recent efforts have been directed to better understanding the role of brain innate immunity, and particularly of microglia. However, and despite the lack of diversity within brain resident immune cells, the brain border tissues, especially the meninges, harbour a considerable number of different types and subtypes of adaptive and innate immune cells. Alongside microglia, which have taken the centre stage as important players in AD research, there is new and exciting evidence pointing to adaptive immune cells, namely T and B cells found in the brain and its meninges, as important modulators of neuroinflammation and neuronal (dys)function in AD. Importantly, a genuine and functional lymphatic vascular network is present around the brain in the outermost meningeal layer, the dura. The meningeal lymphatics are directly connected to the peripheral lymphatic system in different mammalian species, including humans, and play a crucial role in preserving a "healthy" immune surveillance of the CNS, by shaping immune responses, not only locally at the meninges, but also at the level of the brain tissue. In this review, we will provide a comprehensive view on our current knowledge about the meningeal lymphatic vasculature, emphasizing its described roles in modulating CNS fluid and macromolecule drainage, meningeal and brain immunity, as well as glial and neuronal function in aging and in AD.
Topics: Animals; Humans; Alzheimer Disease; Amyloid beta-Peptides; Genome-Wide Association Study; Meninges; Lymphatic System; Brain; Mammals
PubMed: 37580702
DOI: 10.1186/s13024-023-00645-0 -
Vascular Medicine (London, England) Feb 2016
Topics: Drainage; Humans; Intermittent Pneumatic Compression Devices; Lymphatic System; Lymphedema; Massage; Predictive Value of Tests; Risk Factors; Stockings, Compression; Treatment Outcome
PubMed: 26819350
DOI: 10.1177/1358863X15620852 -
International Angiology : a Journal of... Oct 2020Lymphology is evolving in search of a better management of lymphedema patients, both as to the diagnostic pathway and as to the therapeutic options. Similarly, lymphatic... (Review)
Review
Lymphology is evolving in search of a better management of lymphedema patients, both as to the diagnostic pathway and as to the therapeutic options. Similarly, lymphatic system is involved in a wide spectrum of pathophysiologic processes of most chronic degenerative diseases. Translational medicine integrates the interdisciplinary scientific knowledge to improve diagnostic and therapeutic options in the biomedical field. Inflammation and lymphatic function are regarded as the connecting biochemical factors in most diseases. This review focuses on the scientific publications regarding lymphatic system in connection to psycho-neuroendocrine immunology, hormesis, epigenetics and more generally nutrition and lifestyle. The interaction between lymphology and translational medicine may play a relevant role to improve management of lymphedema on the one hand, and of chronic degenerative diseases on the other.
Topics: Humans; Lymphatic System; Lymphatic Vessels; Lymphedema; Translational Research, Biomedical
PubMed: 32348100
DOI: 10.23736/S0392-9590.20.04333-3 -
Birth Defects Research. Part C, Embryo... Sep 2009The lymphatic system is essential for fluid homeostasis, immune responses, and fat absorption, and is involved in many pathological processes, including tumor metastasis... (Review)
Review
The lymphatic system is essential for fluid homeostasis, immune responses, and fat absorption, and is involved in many pathological processes, including tumor metastasis and lymphedema. Despite its importance, progress in understanding the origins and early development of this system has been hampered by lack of defining molecular markers and difficulties in observing lymphatic cells in vivo and performing genetic and experimental manipulation of the lymphatic system. Recent identification of new molecular markers, new genes with important functional roles in lymphatic development, and new experimental models for studying lymphangiogenesis has begun to yield important insights into the emergence and assembly of this important tissue. This review focuses on the mechanisms regulating development of the lymphatic vasculature during embryogenesis.
Topics: Animals; Endothelial Cells; Gene Expression Regulation, Developmental; Humans; Lymphangiogenesis; Lymphatic System; Lymphatic Vessels; Models, Animal; Signal Transduction; Urodela; Vertebrates; Zebrafish
PubMed: 19750516
DOI: 10.1002/bdrc.20155