Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Impaired Meningeal Lymphatic Flow in NMOSD Patients With Acute Attack.

ABSTRACT: The meningeal lymphatic vessels (mLVs) in central nervous system (CNS) have been validated by rodent and human studies. The mLVs play a vital role in draining soluble molecules and trafficking lymphocytes, antigens and antibodies from CNS into cervical lymph nodes (CLNs). This indicates that mLVs may serve as a link between the CNS and peripheral immune system, perhaps involving in the neuroinflammatory disease. However, the morphology and drainage function of mLVs in patients with neuroinflammatory disease, such as neuromyelitis optica spectrum disorders (NMOSD), remains unexplored. Using the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), we found that slower flow through mLVs along superior sagittal sinus in NMOSD patients with acute attack instead of NMOSD patients in chronic phase. The reduced flow in mLVs correlated with the disease severity evaluated by expanded disability status scale (EDSS). The receiver operating characteristic curve (ROC) indicated DCE-MRI might provide objective evidence to predict the acute relapse of NMOSD through evaluating the function of mLVs. Promoting or restoring the function of mLVs might be a new target for the treatment of NMOSD relapse.

SUBMITTER: Wang X

PROVIDER: S-EPMC8236891 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Impaired meningeal lymphatic vessel development worsens stroke outcome.

Project description:The discovery of meningeal lymphatic vessels (LVs) has sparked interest in identifying their role in diseases of the central nervous system. Similar to peripheral LVs, meningeal LVs depend on vascular endothelial growth factor receptor-3 (VEGFR3) signaling for development. Here we characterize the effect of stroke on meningeal LVs, and the impact of meningeal lymphatic hypoplasia on post-stroke outcomes. We show that photothrombosis (PT), but not transient middle cerebral artery occlusion (tMCAo), induces meningeal lymphangiogenesis in young male C57Bl/J6 mice. We also show that Vegfr3wt/mut mice develop significantly fewer meningeal LVs than Vegfr3wt/wt mice. Again, meningeal lymphangiogenesis occurs in the alymphatic zone lateral to the sagittal sinus only after PT-induced stroke in Vegfr3wt/wt mice. Interestingly, Vegfr3wt/mut mice develop larger stroke volumes than Vegfr3wt/wt mice after tMCAo, but not after PT. Our results reveal differences between PT and tMCAo models of stroke and underscore the need to consider method of stroke induction when investigating the role of meningeal lymphatics. Taken together, our data indicate that ischemic injury can induce the growth of meningeal LVs and that the absence of these LVs can impact post-stroke outcomes.

| S-EPMC7370617 | biostudies-literature

Lymph Flow Induces the Postnatal Formation of Mature and Functional Meningeal Lymphatic Vessels.

Project description:Recently, the presence of lymphatics has been demonstrated and characterized in the dura mater, which is in contrast to the well-accepted view indicating the lack of a classical lymphatic drainage system of the central nervous system (CNS). Moreover, the role of meningeal lymphatics in the pathogenesis of Alzheimer's disease and multiple sclerosis was suggested. However, the possible regulators of the developmental program and function of meningeal lymphatics remain unclear. Here, we aimed at characterizing the lymph flow dependence of the developmental program and function of the meningeal lymphatics. First, we demonstrated that lymphatics present in the dura mater are involved in the uptake and transport of macromolecules from the CNS. Meningeal lymphatics develop during the postnatal period which process involves the maturation of the vessels. The formation of mature meningeal lymphatics coincides with the increase of the drainage of macromolecules from the CNS to the deep cervical lymph nodes. Importantly, the structural remodeling and maturation of meningeal lymphatics is impaired in Plcγ2 -/- mice with reduced lymph flow. Furthermore, macromolecule uptake and transport by the meningeal lymphatics are also affected in Plcγ2 -/- mice. Collectively, lymph flow-induced mechanical forces are required for the postnatal formation of mature and functional meningeal lymphatic vessels. Defining lymph flow-dependence of the development and function of meningeal lymphatics may lead to better understanding of the pathogenesis of neurological diseases including Alzheimer's disease and multiple sclerosis.

| S-EPMC6970982 | biostudies-literature

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-03-10 | GSE217314 | GEO

CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature.

Project description:Neuroinflammatory diseases, such as multiple sclerosis, are characterized by invasion of the brain by autoreactive T cells. The mechanism for how T cells acquire their encephalitogenic phenotype and trigger disease remains, however, unclear. The existence of lymphatic vessels in the meninges indicates a relevant link between the CNS and peripheral immune system, perhaps affecting autoimmunity. Here we demonstrate that meningeal lymphatics fulfill two critical criteria: they assist in the drainage of cerebrospinal fluid components and enable immune cells to enter draining lymph nodes in a CCR7-dependent manner. Unlike other tissues, meningeal lymphatic endothelial cells do not undergo expansion during inflammation, and they express a unique transcriptional signature. Notably, the ablation of meningeal lymphatics diminishes pathology and reduces the inflammatory response of brain-reactive T cells during an animal model of multiple sclerosis. Our findings demonstrate that meningeal lymphatics govern inflammatory processes and immune surveillance of the CNS and pose a valuable target for therapeutic intervention.

| S-EPMC6214619 | biostudies-literature

Development and plasticity of meningeal lymphatic vessels.

Project description:The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect. Surprisingly, in adult mice, the LVs showed regression after VEGF-C or VEGFR3 deletion, administration of the tyrosine kinase inhibitor sunitinib, or expression of VEGF-C/D trap, which also compromised the lymphatic drainage function. Conversely, an excess of VEGF-C induced meningeal lymphangiogenesis. The plasticity and regenerative potential of meningeal LVs should allow manipulation of cerebrospinal fluid drainage and neuropathological processes in the CNS.

| S-EPMC5716035 | biostudies-literature

Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis.

Project description:Traumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model of TBI that mild forms of brain trauma cause severe deficits in meningeal lymphatic drainage that begin within hours and last out to at least one month post-injury. To investigate a mechanism underlying impaired lymphatic function in TBI, we examined how increased intracranial pressure (ICP) influences the meningeal lymphatics. We demonstrate that increased ICP can contribute to meningeal lymphatic dysfunction. Moreover, we show that pre-existing lymphatic dysfunction before TBI leads to increased neuroinflammation and negative cognitive outcomes. Finally, we report that rejuvenation of meningeal lymphatic drainage function in aged mice can ameliorate TBI-induced gliosis. These findings provide insights into both the causes and consequences of meningeal lymphatic dysfunction in TBI and suggest that therapeutics targeting the meningeal lymphatic system may offer strategies to treat TBI.

| S-EPMC7483525 | biostudies-literature

Subdural haematomas drain into the extracranial lymphatic system through the meningeal lymphatic vessels.

Project description:Subdural haematomas (SDHs) are characterized by rapidly or gradually accumulated haematomas between the arachnoid and dura mater. The mechanism of haematoma clearance has not been clearly elucidated until now. The meningeal lymphatic vessel (mLV) drainage pathway is a novel system that takes part in the clearance of waste products in the central nervous system (CNS). This study aimed to explore the roles of the mLV drainage pathway in SDH clearance and its impacting factors. We injected FITC-500D, A488-fibrinogen and autologous blood into the subdural space of mice/rats and found that these substances drained into deep cervical lymph nodes (dCLNs). FITC-500D was also observed in the lymphatic vessels (LYVE+) of the meninges and the dCLNs in mice. The SDH clearance rate in SDH rats that received deep cervical lymph vessel (dCLV) ligation surgery was significantly lower than that in the control group, as evaluated by haemoglobin quantification and MRI scanning. The drainage rate of mLVs was significantly slower after the SDH model was established, and the expression of lymphangiogenesis-related proteins, including LYVE1, FOXC2 and VEGF-C, in meninges was downregulated. In summary, our findings proved that SDH was absorbed through the mLV drainage pathway and that haematomas could inhibit the function of mLVs.

| S-EPMC7023797 | biostudies-literature

Project description:The meningeal lymphatic network—housed within the dural meninges surrounding the brain— is critical for cerebrospinal fluid (CSF) drainage. Through continuous brain interstitial fluid (ISF) mixing with CSF via the glymphatic system, this lymphatic network facilitates the removal of central nervous system (CNS) waste. During aging and in Alzheimer’s disease (AD), attenuated meningeal lymphatic drainage promotes the buildup of toxic misfolded proteins—including amyloid beta—in the CNS. Alleviating this age-related meningeal lymphatic dysfunction represents a promising therapeutic strategy to alleviate AD pathology. However, the mechanisms underlying this lymphatic decline remain elusive. Here we demonstrate that age-related alterations in meningeal immunity contribute to meningeal lymphatic impairment. Single-cell RNA-sequencing of dural lymphatic endothelial cells in aged mice demonstrated a response signature to the cytokine IFNγ, which was elevated in the aged dura due to meningeal T cell accumulation. Chronic elevation of IFNγ in the meninges of young mice via AAV-mediated overexpression altered lymphatic adherans junctions and impaired CSF drainage to deep cervical lymph nodes—comparable to the deficits observed in aged mice. Direct disruption of lymphatic junctions via CSF-delivered VE-Cadherin disrupting antibodies was sufficient to phenocopy impairments in CSF drainage. Therapeutically, IFNγ neutralization in aged mice alleviated age-related impairments in meningeal lymphatic function. These data suggest manipulation of meningeal immunity as a viable therapeutic target to normalize CSF drainage in aged mice and alleviate the pathology in AD mice associated with impaired waste removal.

2023-03-10 | GSE217276 | GEO

2023-03-10 | GSE217312 | GEO

Meningeal lymphatic vessels regulate brain tumor drainage and immunity.

Project description:Recent studies have shown that meningeal lymphatic vessels (MLVs), which are located both dorsally and basally beneath the skull, provide a route for draining macromolecules and trafficking immune cells from the central nervous system (CNS) into cervical lymph nodes (CLNs), and thus represent a potential therapeutic target for treating neurodegenerative and neuroinflammatory diseases. However, the roles of MLVs in brain tumor drainage and immunity remain unexplored. Here we show that dorsal MLVs undergo extensive remodeling in mice with intracranial gliomas or metastatic melanomas. RNA-seq analysis of MLV endothelial cells revealed changes in the gene sets involved in lymphatic remodeling, fluid drainage, as well as inflammatory and immunological responses. Disruption of dorsal MLVs alone impaired intratumor fluid drainage and the dissemination of brain tumor cells to deep CLNs (dCLNs). Notably, the dendritic cell (DC) trafficking from intracranial tumor tissues to dCLNs decreased in mice with defective dorsal MLVs, and increased in mice with enhanced dorsal meningeal lymphangiogenesis. Strikingly, disruption of dorsal MLVs alone, without affecting basal MLVs or nasal LVs, significantly reduced the efficacy of combined anti-PD-1/CTLA-4 checkpoint therapy in striatal tumor models. Furthermore, mice bearing tumors overexpressing VEGF-C displayed a better response to anti-PD-1/CTLA-4 combination therapy, and this was abolished by CCL21/CCR7 blockade, suggesting that VEGF-C potentiates checkpoint therapy via the CCL21/CCR7 pathway. Together, the results of our study not only demonstrate the functional aspects of MLVs as classic lymphatic vasculature, but also highlight that they are essential in generating an efficient immune response against brain tumors.

| S-EPMC7054407 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data