title: Expression of Lymphatic Markers in the Adult Rat Spinal Cord.
abstract: Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with Iba1, the LYVE-1+ cell population likely represents a macrophage subpopulation, while a significant fraction of PROX1+ cells belong to the oligodendrocytic lineage based on their distribution and the expression of OLIG2. The response of these LYVE-1+ and PROX1+ cell subpopulations to pathological conditions, especially in spinal cord inflammatory conditions, needs to be further elucidated.
authors.affiliation: University Clinic of Ophthalmology and Optometry, Research Program for Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University Salzburg, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaser-Eichberger
authors.affiliation: University Clinic of Ophthalmology and Optometry, Research Program for Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical UniversitySalzburg, Austria; Institute of Anatomy, Paracelsus Medical UniversitySalzburg, Austria.
authors.forename: Falk
authors.initials: F
authors.lastname: Schroedl
authors.affiliation: Institute of Experimental Neuroregeneration, Paracelsus Medical UniversitySalzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg, (SCI-TReCS), Paracelsus Medical UniversitySalzburg, Austria.
authors.forename: Lara
authors.initials: L
authors.lastname: Bieler
authors.affiliation: University Clinic of Ophthalmology and Optometry, Research Program for Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University Salzburg, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Trost
authors.affiliation: University Clinic of Ophthalmology and Optometry, Research Program for Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University Salzburg, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bogner
authors.affiliation: University Clinic of Ophthalmology and Optometry, Research Program for Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University Salzburg, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Runge
authors.affiliation: Institute of Tendon and Bone Regeneration, Paracelsus Medical UniversitySalzburg, Austria; Austrian Cluster for Tissue RegenerationVienna, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Tempfer
authors.affiliation: Institute of Experimental Neuroregeneration, Paracelsus Medical UniversitySalzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg, (SCI-TReCS), Paracelsus Medical UniversitySalzburg, Austria.
authors.forename: Pia
authors.initials: P
authors.lastname: Zaunmair
authors.affiliation: Institute of Experimental Neuroregeneration, Paracelsus Medical UniversitySalzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg, (SCI-TReCS), Paracelsus Medical UniversitySalzburg, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Kreutzer
authors.affiliation: Institute of Tendon and Bone Regeneration, Paracelsus Medical UniversitySalzburg, Austria; Austrian Cluster for Tissue RegenerationVienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Traweger
authors.affiliation: University Clinic of Ophthalmology and Optometry, Research Program for Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University Salzburg, Austria.
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Reitsamer
authors.affiliation: Institute of Experimental Neuroregeneration, Paracelsus Medical UniversitySalzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center Salzburg, (SCI-TReCS), Paracelsus Medical UniversitySalzburg, Austria.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Couillard-Despres
keywords: Iba1; LYVE-1; OLIG2; PROX1; lymphatics; macrophage; spinal cord; spinal cord injury