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      Anatomy and function of the vertebral column lymphatic network in mice

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          Abstract

          Cranial lymphatic vessels (LVs) are involved in the transport of fluids, macromolecules and central nervous system (CNS) immune responses. Little information about spinal LVs is available, because these delicate structures are embedded within vertebral tissues and difficult to visualize using traditional histology. Here we show an extended vertebral column LV network using three-dimensional imaging of decalcified iDISCO +-clarified spine segments. Vertebral LVs connect to peripheral sensory and sympathetic ganglia and form metameric vertebral circuits connecting to lymph nodes and the thoracic duct. They drain the epidural space and the dura mater around the spinal cord and associate with leukocytes. Vertebral LVs remodel extensively after spinal cord injury and VEGF-C-induced vertebral lymphangiogenesis exacerbates the inflammatory responses, T cell infiltration and demyelination following focal spinal cord lesion. Therefore, vertebral LVs add to skull meningeal LVs as gatekeepers of CNS immunity and may be potential targets to improve the maintenance and repair of spinal tissues.

          Abstract

          The lymphatic vasculature is essential to maintain fluid homeostasis and immune surveillance, including in the brain where lymphatic vessels were only recently identified. Here, Jacob et al. provide an anatomical map of lymphatic vessels in the vertebral column, where they find these contribute to fluid drainage and immune responses.

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          Most cited references34

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          Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes.

          Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available.
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            Systematic literature review of imaging features of spinal degeneration in asymptomatic populations.

            Degenerative changes are commonly found in spine imaging but often occur in pain-free individuals as well as those with back pain. We sought to estimate the prevalence, by age, of common degenerative spine conditions by performing a systematic review studying the prevalence of spine degeneration on imaging in asymptomatic individuals.
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              Mechanisms of lymphatic metastasis.

              Malignant tumors release growth factors such as VEGF-C to induce lymphatic vessel expansion (lymphangiogenesis) in primary tumors and in draining sentinel LNs, thereby promoting LN metastasis. Surprising recent evidence suggests that lymphatic vessels do not merely represent passive channels for tumor spread, but that they may actively promote tumor cell recruitment to LNs, cancer stem cell survival, and immune modulation. New imaging approaches allow the sensitive visualization of the earliest LN metastases and the quantitative, noninvasive measurement of the function of tumor-draining lymphatic vessels, with potential applications in the development of biomarkers for prognosis and measurement of therapeutic response.
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                Author and article information

                Contributors
                jean-leon.thomas@yale.edu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                9 October 2019
                9 October 2019
                2019
                : 10
                : 4594
                Affiliations
                [1 ]ISNI 0000 0004 0620 5939, GRID grid.425274.2, Université Pierre et Marie Curie Paris 06 UMRS1127, Sorbonne Université, Institut du Cerveau et de la Moelle Epinière, ; Paris, France
                [2 ]ISNI 0000000419368710, GRID grid.47100.32, Department of Neurology, , Yale University School of Medicine, ; New Haven, CT 06511 USA
                [3 ]ISNI 0000 0004 0495 1460, GRID grid.462416.3, INSERM U970, Paris Cardiovascular Research Center, ; 56 Rue Leblanc, 75015 Paris, France
                [4 ]ISNI 0000 0001 2294 473X, GRID grid.8536.8, Institute of Biomedical Sciences, , Federal University of Rio de Janeiro, ; Rio de Janeiro, Brazil
                [5 ]ISNI 0000 0004 0410 2071, GRID grid.7737.4, Wihuri Research Institute and Translational Cancer Medicine Program, Faculty of Medicine, , University of Helsinki, ; Helsinki, Finland
                [6 ]Ecole Nationale Supérieure d’Art de la Villa Arson, 06100 Nice, France
                [7 ]ISNI 0000000419368710, GRID grid.47100.32, Department of Immunology, , Yale University School of Medicine, ; New Haven, CT 06510-3221 USA
                [8 ]ISNI 0000000419368710, GRID grid.47100.32, Cardiovascular Research Center and the Department of Cellular and Molecular Physiology, , Yale University School of Medicine, ; New Haven, CT 06510-3221 USA
                Author information
                http://orcid.org/0000-0002-5772-5999
                http://orcid.org/0000-0001-7761-1684
                http://orcid.org/0000-0001-5448-5865
                http://orcid.org/0000-0003-2642-4402
                Article
                12568
                10.1038/s41467-019-12568-w
                6785564
                31597914
                7d6c66ce-8547-4904-99aa-6a19c72df6f5
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 8 August 2018
                : 11 September 2019
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                fluorescence imaging,spine regulation and structure,cardiovascular biology
                Uncategorized
                fluorescence imaging, spine regulation and structure, cardiovascular biology

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