1,721,039 research outputs found
Cerebrospinal fluid draining lymphatics in health and disease: advances and controversies
Full text linkThe meninges, consisting of the dura, arachnoid and pia mater that surround the brain and spinal cord, have been recognized from the earliest anatomical studies. First identified in 1787, lymphatic vessels in the dura are now receiving greater attention as their contribution to cerebrospinal fluid (CSF) clearance in diverse neurological conditions is being investigated. New methods have increased the understanding of dural lymphatics, but much is still being learned about their heterogeneity, intracranial and extracranial connections, and factors that govern their functions and maintenance. Current research is striving to understand the regulation of CSF drainage and influence of brain antigen and immune cell transit through dural lymphatics on aging impairments and the severity of neurodegenerative and neuroimmune diseases, traumatic brain injury, stroke and other neurological disorders. Achieving these goals should lead to safe and effective methods for manipulating CSF clearance through dural lymphatics for therapeutic benefit
Molecular mechanisms and imaging of lymphatic metastasis.
No full textIn many types of cancer, tumors metastasize through the lymphatic system to draining lymph nodes. These sentinel lymph nodes have gained increased attention as a prognostic indicator for the severity of the disease, leading to the sentinel lymph node mapping and biopsy procedure to be accepted as standard-of-care for breast cancer and melanoma. However, many limitations exist with this procedure resulting in high false negative rates. In this review we highlight the new advances in the understanding of the molecular mechanisms of lymphangiogenesis and tumor metastasis that may lead to improved strategies in the detection of the sentinel lymph nodes and therapeutic interventions to prevent further tumor spread. In addition, advances in imaging technology are allowing new approaches for anatomical mapping of lymphatic drainage patterns and molecular imaging strategies that may improve detection of metastatic tumor cells within sentinel lymph nodes
Cerebrospinal fluid outflow: a review of the historical and contemporary evidence for arachnoid villi, perineural routes, and dural lymphatics
Full text linkCerebrospinal fluid (CSF) is produced by the choroid plexuses within the ventricles of the brain and circulates through the subarachnoid space of the skull and spinal column to provide buoyancy to and maintain fluid homeostasis of the brain and spinal cord. The question of how CSF drains from the subarachnoid space has long puzzled scientists and clinicians. For many decades, it was believed that arachnoid villi or granulations, outcroppings of arachnoid tissue that project into the dural venous sinuses, served as the major outflow route. However, this concept has been increasingly challenged in recent years, as physiological and imaging evidence from several species has accumulated showing that tracers injected into the CSF can instead be found within lymphatic vessels draining from the cranium and spine. With the recent high-profile rediscovery of meningeal lymphatic vessels located in the dura mater, another debate has emerged regarding the exact anatomical pathway(s) for CSF to reach the lymphatic system, with one side favoring direct efflux to the dural lymphatic vessels within the skull and spinal column and another side advocating for pathways along exiting cranial and spinal nerves. In this review, a summary of the historical and contemporary evidence for the different outflow pathways will be presented, allowing the reader to gain further perspective on the recent advances in the field. An improved understanding of this fundamental physiological process may lead to novel therapeutic approaches for a wide range of neurological conditions, including hydrocephalus, neurodegeneration and multiple sclerosis
Clearance of erythrocytes from the subarachnoid space through cribriform plate lymphatics in female mice.
Full text linkBACKGROUND
Atraumatic subarachnoid haemorrhage (SAH) is associated with high morbidity and mortality. Proposed mechanisms for red blood cell (RBC) clearance from the subarachnoid space (SAS) are erythrolysis, erythrophagocytosis or through efflux along cerebrospinal fluid (CSF) drainage routes. We aimed to elucidate the mechanisms of RBC clearance from the SAS to identify targetable efflux pathways.
METHODS
Autologous fluorescently-labelled RBCs along with PEGylated 40 kDa near-infrared tracer (P40D800) were infused via the cisterna magna (i.c.m.) in female reporter mice for lymphatics or for resident phagocytes. Drainage pathways for RBCs to extracranial lymphatics were evaluated by in vivo and in situ near-infrared imaging and by immunofluorescent staining on decalcified cranial tissue or dural whole-mounts.
FINDINGS
RBCs drained to the deep cervical lymph nodes 15 min post i.c.m. infusion, showing similar dynamics as P40D800 tracer. Postmortem in situ imaging and histology showed perineural accumulations of RBCs around the optic and olfactory nerves. Numerous RBCs cleared through the lymphatics of the cribriform plate, whilst histology showed no relevant fast RBC clearance through dorsal dural lymphatics or by tissue-resident macrophage-mediated phagocytosis.
INTERPRETATION
This study provides evidence for rapid RBC drainage through the cribriform plate lymphatic vessels, whilst neither fast RBC clearance through dorsal dural lymphatics nor through spinal CSF efflux or phagocytosis was observed. Similar dynamics of P40D800 and RBCs imply open pathways for clearance that do not impose a barrier for RBCs. This finding suggests further evaluation of the cribriform plate lymphatic function and potential pharmacological targeting in models of SAH.
FUNDING
Swiss National Science Foundation (310030_189226), SwissHeart (FF191155)
Central nervous system zoning: How brain barriers establish subdivisions for CNS immune privilege and immune surveillance.
Full text linkThe central nervous system (CNS) coordinates all our body functions. Neurons in the CNS parenchyma achieve this computational task by high speed communication via electrical and chemical signals and thus rely on a strictly regulated homeostatic environment, which does not tolerate uncontrolled entry of blood components including immune cells. The CNS thus has a unique relationship with the immune system known as CNS immune privilege. Previously ascribed to the presence of blood-brain barriers and the lack of lymphatic vessels in the CNS parenchyma prohibiting, respectively, efferent and afferent connections with the peripheral immune system, it is now appreciated that CNS immune surveillance is ensured by cellular and acellular brain barriers that limit immune cell and mediator accessibility to specific compartments at the borders of the CNS. CNS immune privilege is established by a brain barriers anatomy resembling the architecture of a medieval castle surrounded by two walls bordering a castle moat. Built for protection and defense this two-walled rampart at the outer perimeter of the CNS parenchyma allows for accommodation of different immune cell subsets and efficient monitoring of potential danger signals derived from inside or outside of the CNS parenchyma in addition to the efficient mounting of immune responses within the subarachnoid or perivascular spaces while leaving the CNS parenchyma relatively undisturbed. We here propose that CNS immune privilege rests on the proper function of the brain barriers, which allow for CNS immune surveillance but prohibit activation of immune responses from the CNS parenchyma unless it is directly injured. This article is protected by copyright. All rights reserved
Translational perspectives on psoriatic arthritis.
No full textThe term psoriatic disease encompasses the array of disorders (arthritis, inflammatory bowel disease, uveitis, obesity, metabolic syndrome, type II diabetes, and cardiovascular disease) that are associated with psoriasis. Psoriatic arthritis (PsA) is present in about 25% of patients with psoriasis; in most cases, the psoriasis precedes joint disease by about 10 years. Previous studies revealed that osteoclast precursors (OCP) are elevated in PsA and that the frequency of these circulating cells correlates with bone destruction. More recently OCP were found to be increased also in early rheumatoid arthritis and in 25% of psoriasis patients without arthritis. Bone marrow edema, observed on magnetic resonance imaging, in PsA represents infiltration of underlying marrow with inflammatory cells based on studies in transgenic tumor necrosis factor (TNF) arthritis murine models. Studies in the TNF transgenic mouse model also revealed that changes in lymph node volume precede joint flare. These translational studies point to potential biomarkers of arthritis in psoriasis patients and generate alternative hypotheses to explain the events that lead to arthritic flare
Watching lymphatic vessels grow by making them glow
No full textA novel imaging technique for visualizing the growth of lymphatic vessels in the cornea is summarized. Comparison to existing lymphatic imaging approaches and perspectives for future research are described
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