scholarly journals Neuroinflammation creates an immune regulatory niche at the meningeal lymphatic vasculature near the cribriform plate.

2021 ◽  
Author(s):  
Zsuzsanna Fabry ◽  
Martin Hsu ◽  
Collin Laaker ◽  
Andy Madrid ◽  
Melinda Herbath ◽  
...  
Keyword(s):  
Immune Surveillance ◽  
Lymphatic Vessels ◽  
Cribriform Plate ◽  
Autoimmune Encephalomyelitis ◽  
New Therapeutic Approaches ◽  
Unrestricted Access ◽  
Drain Fluid ◽  
Lymphatic Vasculature ◽  
And Function ◽  
The Brain

Abstract Meningeal lymphatic vessels residing in the dural layer above the sinuses of the brain, meninges at the base of the brain, and near the cribriform plate have all been shown to drain fluid, cells, and antigens. We have previously reported that meningeal lymphatics near the cribriform plate undergo VEGFR3-dependent lymphangiogenesis during experimental autoimmune encephalomyelitis (EAE) to facilitate excess drainage. Using single-cell RNA sequencing (scRNA-seq), we report that neuroinflammation changes the phenotype and function of cribriform plate lymphatic endothelial cells (cpLECs). Upregulation of genes involved in antigen presentation, adhesion to leukocytes, and immunoregulatory molecules were verified by flow cytometry and functional assays. The inflamed cpLECs retain dendritic cells and to lesser extent CD4 T cells, creating an immune-regulatory niche that represents a previously underappreciated interface in the regulation of neuroinflammation. Additionally, the discontinuity of the arachnoid membrane near cpLECs provides unrestricted access to the cerebrospinal fluid (CSF) for immune surveillance. These findings may lead to new therapeutic approaches to neuroinflammatory diseases.

scholarly journals Brain lymphatic drainage system – visualization opportunities and current state of the art

2020 ◽  
Vol 9 (3) ◽  
pp. 81-89
Author(s):  
G. S. Yankova ◽  
O. B. Bogomyakova
Keyword(s):  
Neurodegenerative Diseases ◽  
Immune Surveillance ◽  
Lymphatic Vessels ◽  
Drainage System ◽  
Lymphatic Drainage ◽  
Waste Products ◽  
Glymphatic System ◽  
Age Related ◽  
The Central Nervous System ◽  
The Brain

The lymphatic drainage system of the brain is assumed to consist of the lymphatic system and a network of meningeal lymphatic vessels. This system supports brain homeostasis, participates in immune surveillance and presents a new therapeutic target in the treatment of neurological disorders.The article analyzes and systematizes data on the brain lymphatic drainage system. The key components of this system are considered: recently described meningeal lymphatic vessels and their relationship with the glymphatic system, which provides perfusion of the central nervous system with cerebrospinal and interstitial fluids. The lymphatic drainage system helps to maintain water and ion balances of the interstitial fluid and to remove metabolic waste products, assists in reabsorption of macromolecules. Disorders in its work play a crucial role in age-related changes in the brain, the pathogenesis of neurovascular and neurodegenerative diseases, as well as injuries and brain tumors. The review also presents the results of human studies concerning the presence, anatomy and structure of meningeal lymphatic vessels and the glymphatic system. The discovery of the brain lymphatic drainage system has not only changed our understanding of cerebrospinal fluid circulation, but also contributed to understanding the pathology and mechanisms of neurodegenerative diseases.

scholarly journals Extracellular Membrane Vesicles as Vehicles for Brain Cell-to-Cell Interactions in Physiological as well as Pathological Conditions

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Gabriella Schiera ◽  
Carlo Maria Di Liegro ◽  
Italia Di Liegro
Keyword(s):  
Cancer Cells ◽  
Tau Protein ◽  
Immune Surveillance ◽  
Noncoding Rnas ◽  
Membrane Vesicles ◽  
Brain Cell ◽  
Pathological Conditions ◽  
And Function ◽  
The Brain ◽  
Diagnosis Of Diseases

Extracellular vesicles are involved in a great variety of physiological events occurring in the nervous system, such as cross talk among neurons and glial cells in synapse development and function, integrated neuronal plasticity, neuronal-glial metabolic exchanges, and synthesis and dynamic renewal of myelin. Many of these EV-mediated processes depend on the exchange of proteins, mRNAs, and noncoding RNAs, including miRNAs, which occurs among glial and neuronal cells. In addition, production and exchange of EVs can be modified under pathological conditions, such as brain cancer and neurodegeneration. Like other cancer cells, brain tumours can use EVs to secrete factors, which allow escaping from immune surveillance, and to transfer molecules into the surrounding cells, thus transforming their phenotype. Moreover, EVs can function as a way to discard material dangerous to cancer cells, such as differentiation-inducing proteins, and even drugs. Intriguingly, EVs seem to be also involved in spreading through the brain of aggregated proteins, such as prions and aggregated tau protein. Finally, EVs can carry useful biomarkers for the early diagnosis of diseases. Herein we summarize possible roles of EVs in brain physiological functions and discuss their involvement in the horizontal spreading, from cell to cell, of both cancer and neurodegenerative pathologies.

scholarly journals Lymphatic Senescence: Current Updates and Perspectives

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 293
Author(s):  
Sebastian Lucio Filelfi ◽  
Alberto Onorato ◽  
Bianca Brix ◽  
Nandu Goswami
Keyword(s):  
Lymphatic System ◽  
Light Exposure ◽  
Contractile Activity ◽  
Lymphatic Vessels ◽  
Nerve Fibers ◽  
Treatment Modalities ◽  
Lymphatic Flow ◽  
Lymphatic Vasculature ◽  
And Function ◽  
The Impact

Lymphatic flow is necessary for maintenance of vital physiological functions in humans and animals. To carry out optimal lymphatic flow, adequate contractile activity of the lymphatic collectors is necessary. Like in all body systems, aging has also an effect on the lymphatic system. However, limited knowledge is available on how aging directly affects the lymphatic system anatomy, physiology and function. We investigated how senescence leads to alterations in morphology and function of the lymphatic vessels. We used the strategy of a review to summarize the scientific literature of studies that have been published in the area of lymphatic senescence. Searches were carried out on PubMed and Web of Science using predefined search queries. We obtained an initial set of 1060 publications. They were filtered to 114 publications based on strict inclusion and exclusion criteria. Finally, the most appropriate 57 studies that specifically addressed lymphatic senescence have been selected for the preparation of this review. Analysis of the literature showed that lymphatic senescence is associated with alterations in lymphatic muscles and nerve fibers, lymphatic glycocalyx function of lymphatic endothelial cells, effects of chronic ultraviolet light exposure and oxidative stress as well as changes in lymphatic pump, acute inflammation responses and immune function. The current review underscores the relevance of the understudied area of lymphatic senescence. Continued research on the impact of aging on the structure and function of the lymphatic vasculature is needed to provide further insights to develop innovative clinical diagnostic—and treatment—modalities as well as to reduce the morbidity associated with diseases related to the lymphatic system.

scholarly journals Neuroinflammation alters the phenotype of lymphangiogenic vessels near the cribriform plate

2020 ◽  
Author(s):  
Martin Hsu ◽  
Andy Madrid ◽  
Yun Hwa Choi ◽  
Collin Laaker ◽  
Melinda Herbath ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Lymphatic Vessels ◽  
Cribriform Plate ◽  
Direct Access ◽  
Functional Changes ◽  
Ifn Γ ◽  
Dynamic Structures ◽  
Cell Trajectory ◽  
The Brain

AbstractMeningeal lymphatic vessels residing in the dural layer surrounding the dorsal regions of the brain, basal regions, and near the cribriform plate have all been implicated in the management of neuroinflammation and edema. Interestingly, only the lymphatic vessels near the cribriform plate undergo functional lymphangiogenesis in a mouse model of Multiple Sclerosis, suggesting these particular lymphatics uniquely undergo dynamic changes in response to neuroinflammation and may have distinct access to pro-lymphangiogenic factors in the CNS. However, it is unknown if these newly formed lymphangiogenic vessels are functionally similar to steady-state or if they have any other functional changes during neuroinflammation. In this study, we generated a novel protocol to isolate lymphatic endothelial cells from the cribriform plate for single cell analysis. We demonstrate that neuroinflammation-induced lymphangiogenic vessels undergo unique changes, including the capture of CNS-derived antigens, upregulation of adhesion and immune-modulatory molecules to interact with dendritic cells, and display IFN-γ dependent changes in response to the microenvironment. Single-cell trajectory analysis showed that cribriform plate lymphangiogenic vessels are post-proliferative and not generated from trans-differentiation of myeloid cells. Additionally, we show that these lymphangiogenic vessels have access to a CSF reservoir, express the water pore Aquaporin-1, and may have direct access to the CSF due to gaps in the arachnoid epithelial layer separating the dura from the subarachnoid space. These data characterize cribriform plate lymphatics and demonstrate that these vessels are dynamic structures that engage in leukocyte interactions, antigen sampling, and undergo expansion to drain excess fluid during neuroinflammation. Neuroinflammation not only induces efficient drainage of CSF but also alters the functions of lymphatic vessels near the cribriform plate.

Lymphangiogenesis in renal diseases: passive bystander or active participant?

2014 ◽  
Vol 16 ◽  
Author(s):  
Saleh Yazdani ◽  
Gerjan Navis ◽  
Jan-Luuk Hillebrands ◽  
Harry van Goor ◽  
Jacob van den Born
Keyword(s):  
Kidney Diseases ◽  
Immune Surveillance ◽  
Lymphatic Vessels ◽  
Therapeutic Interventions ◽  
Lymph Vessel ◽  
Renal Diseases ◽  
Tissue Remodelling ◽  
The Past ◽  
Lymphatic Vasculature ◽  
Fibrotic Disorders

Lymphatic vessels (LVs) are involved in a number of physiological and pathophysiological processes such as fluid homoeostasis, immune surveillance, and resolution of inflammation and wound healing. Lymphangiogenesis, the outgrowth of existing LVs and the formation of new ones, has received increasing attention over the past decade on account of its prominence in organ physiology and pathology, which has been enabled by the development of specific tools to study lymph vessel functions. Several studies have been devoted to renal lymphatic vasculature and lymphangiogenesis in kidney diseases, such as chronic renal transplant dysfunction, primary renal fibrotic disorders, proteinuria, diabetic nephropathy and renal inflammation. This review describes the most recent findings on lymphangiogenesis, with a specific focus on renal lymphangiogenesis and its impact on renal diseases. We suggest renal lymphatics as a possible target for therapeutic interventions in renal medicine to dampen tubulointerstitial tissue remodelling and improve renal functioning.

scholarly journals A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules

2015 ◽  
Vol 212 (7) ◽  
pp. 991-999 ◽  
Author(s):  
Aleksanteri Aspelund ◽  
Salli Antila ◽  
Steven T. Proulx ◽  
Tine Veronica Karlsen ◽  
Sinem Karaman ◽  
...  
Keyword(s):  
Subarachnoid Space ◽  
Interstitial Fluid ◽  
Vascular System ◽  
Lymphatic Vessels ◽  
Cervical Lymph Nodes ◽  
Brain Interstitial Fluid ◽  
Lymphatic Vasculature ◽  
The Central Nervous System ◽  
Base Of The Skull ◽  
The Brain

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.

The glymphatic system and meningeal lymphatics of the brain: new understanding of brain clearance

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Galina Yankova ◽  
Olga Bogomyakova ◽  
Andrey Tulupov
Keyword(s):  
Neurodegenerative Diseases ◽  
Brain Injuries ◽  
Immune Surveillance ◽  
Lymphatic Vessels ◽  
Drainage System ◽  
Waste Products ◽  
Glymphatic System ◽  
System A ◽  
Age Related ◽  
The Brain

Abstract The glymphatic system and meningeal lymphatics have recently been characterized. Glymphatic system is a glia-dependent system of perivascular channels, and it plays an important role in the removal of interstitial metabolic waste products. The meningeal lymphatics may be a key drainage route for cerebrospinal fluid into the peripheral blood, may contribute to inflammatory reaction and central nervous system (CNS) immune surveillance. Breakdowns and dysfunction of the glymphatic system and meningeal lymphatics play a crucial role in age-related brain changes, the pathogenesis of neurovascular and neurodegenerative diseases, as well as in brain injuries and tumors. This review discusses the relationship recently characterized meningeal lymphatic vessels with the glymphatic system, which provides perfusion of the CNS with cerebrospinal and interstitial fluids. The review also presents the results of human studies concerning both the presence of meningeal lymphatics and the glymphatic system. A new understanding of how aging, medications, sleep and wake cycles, genetic predisposition, and even body posture affect the brain drainage system has not only changed the idea of brain fluid circulation but has also contributed to an understanding of the pathology and mechanisms of neurodegenerative diseases.

scholarly journals New insights about the lymphatic vasculature in cardiovascular diseases

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1811 ◽  
Author(s):  
Xiaolei Liu ◽  
Guillermo Oliver
Keyword(s):  
Blood Vessels ◽  
Cardiac Tissue ◽  
Lymphatic Vessels ◽  
Tissue Fluid ◽  
Major Focus ◽  
The Past ◽  
Growing Body ◽  
Lymphatic Vasculature ◽  
Coronary Blood Vessels ◽  
And Function

The heart contains a complex network of blood and lymphatic vessels. The coronary blood vessels provide the cardiac tissue with oxygen and nutrients and have been the major focus of research for the past few decades. Cardiac lymphatic vessels, which consist of lymphatic capillaries and collecting lymphatic vessels covering all layers of the heart, transport excess fluid from the interstitium and play important roles in maintaining tissue fluid balance. Unlike for the coronary blood vessels, until a few years ago, not much information was available on the origin and function of the cardiac-associated lymphatic vasculature. A growing body of evidence indicates that cardiac lymphatic vessels (lymphatics) may serve as a therapeutic cardiovascular target.

scholarly journals The Role of Lymphatic Marker Prox-1 in Relation to Brain Tumours

2021 ◽  
Vol 65 (4) ◽  
pp. 72-78
Author(s):  
J. Teleky ◽  
J. Király
Keyword(s):  
Brain Tumours ◽  
Current Knowledge ◽  
Treatment Options ◽  
Lymphatic Vessels ◽  
Homeobox Gene ◽  
Lymphatic Vasculature ◽  
Lymphatic Development ◽  
The Central Nervous System ◽  
The Brain

Abstract The homeobox gene, Prox-1 is a transcription factor essential for lymphatic development (lymphangiogenesis) during embryogenesis. It also performs different functions in various tissues such as: retina, lens, liver, pancreas and the central nervous system. Intense expression of Prox-1 has been demonstrated in the developing spinal cord and brain. In adulthood its expression continues in the hippocampus and cerebellum. In adult tissues the process of lymphatic vasculature formation is accompanied under certain pathological conditions such as inflammation, tissue repair and tumour growth. Prox-1 expression is typical for lymphatic vessels; thus it belongs to one of the most specific and widely used mammalian lymphatic endothelial marker in the detection of lymphangiogenesis and lymphatic vessel invasion in oncogenesis. It has been shown that Prox-1 is involved in cancer development and progression. It’s tumour suppressive and oncogenic properties are proven in several human cancers, including brain tumours. Among all body cancers the brain tumours represent the most feared tumours with very limited treatment options and a poor diagnosis. The aim of this paper was to show the current knowledge of the gene Prox-1 with an emphasis on brain tumours, especially in gliomas.

scholarly journals The brain’sglymphatic system:physiological anatomy and clinical perspectives

2018 ◽  
Vol 10 (4) ◽  
pp. 94-100 ◽  
Author(s):  
V. N. Nikolenko ◽  
M. V. Oganesyan ◽  
N. N. Yakhno ◽  
E. A. Orlov ◽  
E. E. Porubayeva ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Cerebral Arteries ◽  
Lymphatic Vessels ◽  
Circulatory System ◽  
Brain Parenchyma ◽  
Special Role ◽  
Close Link ◽  
New Therapeutic Approaches ◽  
The Central Nervous System ◽  
The Brain

The recently discovered glymphatic system (GS) ensures the efficient clearance of interstitial fluid and soluble compounds from the central nervous system into cerebrospinal fluid (CSF), which compensates for the lack of conventional lymphatic vessels in the brain parenchyma. This unique anatomical and physiological phenomenon had been unknown until 2012. GS lacks inherent proper vessels Р the current of CSF and interstitial fluid is carried out directly inside the arterial walls (the perivascular pathway) or near the walls of the cerebral arteries and veins (the paravascular pathway). Current biorheological technologies could establish a special role of aquaporin-4 in the filtration of CSF and interstitial fluid. The close link between GS and the CSF circulatory system allows the established views on fluid dynamics within the brain to be reconsidered. The discovery of GS can contribute to our understanding of the pathogenesis of increased intracranial pressure and neurodegenerative diseases, as well as to the elaboration of new therapeutic approaches to their treatment.

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