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.
Highlights
Cranial lymphatic vessels (LVs) are involved in the transport of fluids, macromolecules and central nervous system (CNS) immune responses
Immune and neural cell compartments within the intact vertebral column, segments of 2–4 vertebrae were dissected together with the surrounding muscle tissue and decalcified in Morse’s solution23. iDISCO+ tissue clearing and immunolabeling followed by light-sheet fluorescence microscope (LSFM) imaging were used for 3D-reconstruction of the spinal LV network
The iDISCO+ protocol was first applied to the thoracic spine, with the goal to characterize the 3D anatomy of vertebral lymphatic vessels (vLVs)
Summary
Cranial lymphatic vessels (LVs) are involved in the transport of fluids, macromolecules and central nervous system (CNS) immune responses. The meningeal lymphatic vasculature develops later than the rest of the lymphatic network, first appearing at birth in the basal parts of the skull, expanding during the neonatal period along dural blood vessels whose vascular smooth muscle cells supply the VEGF-C14. Immuno-histology on whole-mount preparations or cryosections showed that, during the first weeks after birth, LVs developed a large network closely attached to the vertebral column[14] These vertebral lymphatic vessels (vLVs) occur mainly in intervertebral spaces, having different morphology ventrally and dorsally, as well as along spinal nerve rami when exciting the spinal canal
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