title: Proteomic Analysis of the Spatio-temporal Based Molecular Kinetics of Acute Spinal Cord Injury Identifies a Time- and Segment-specific Window for Effective Tissue Repair.
abstract: Spinal cord injury (SCI) represents a major debilitating health issue with a direct socioeconomic burden on the public and private sectors worldwide. Although several studies have been conducted to identify the molecular progression of injury sequel due from the lesion site, still the exact underlying mechanisms and pathways of injury development have not been fully elucidated. In this work, based on OMICs, 3D matrix-assisted laser desorption ionization (MALDI) imaging, cytokines arrays, confocal imaging we established for the first time that molecular and cellular processes occurring after SCI are altered between the lesion proximity, i.e. rostral and caudal segments nearby the lesion (R1-C1) whereas segments distant from R1-C1, i.e. R2-C2 and R3-C3 levels coexpressed factors implicated in neurogenesis. Delay in T regulators recruitment between R1 and C1 favor discrepancies between the two segments. This is also reinforced by presence of neurites outgrowth inhibitors in C1, absent in R1. Moreover, the presence of immunoglobulins (IgGs) in neurons at the lesion site at 3 days, validated by mass spectrometry, may present additional factor that contributes to limited regeneration. Treatment in vivo with anti-CD20 one hour after SCI did not improve locomotor function and decrease IgG expression. These results open the door of a novel view of the SCI treatment by considering the C1 as the therapeutic target.
authors.affiliation: From the ‡Univ. Lille, Inserm, U-1192 - Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, F-59000 Lille, France; §Institute of Neurobiology, Slovak Academy of Sciences, Center of Excellence for Brain Research, Soltesovej 4-6 Kosice, Slovakia; §§Department of Anatomy, Histology and Physiology, University of Veterinary Medicine and Pharmacy in Kosice, Komenskeho 73, 041 81 Kosice, Slovakia Michel.salzet@univ-lille1.fr.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Devaux
authors.affiliation: From the ‡Univ. Lille, Inserm, U-1192 - Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, F-59000 Lille, France; §Institute of Neurobiology, Slovak Academy of Sciences, Center of Excellence for Brain Research, Soltesovej 4-6 Kosice, Slovakia; §§Department of Anatomy, Histology and Physiology, University of Veterinary Medicine and Pharmacy in Kosice, Komenskeho 73, 041 81 Kosice, Slovakia.
authors.forename: Dasa
authors.initials: D
authors.lastname: Cizkova
authors.affiliation: From the ‡Univ. Lille, Inserm, U-1192 - Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, F-59000 Lille, France;
authors.forename: Jusal
authors.initials: J
authors.lastname: Quanico
authors.affiliation: From the ‡Univ. Lille, Inserm, U-1192 - Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, F-59000 Lille, France;
authors.forename: Julien
authors.initials: J
authors.lastname: Franck
authors.affiliation: ¶Inserm U-1060, CarMeN Laboratory, Banque de Tissus et de Cellules des Hospices Civils de Lyon, Université Lyon-1, France;
authors.forename: Serge
authors.initials: S
authors.lastname: Nataf
authors.affiliation: ¶Inserm U-1060, CarMeN Laboratory, Banque de Tissus et de Cellules des Hospices Civils de Lyon, Université Lyon-1, France;
authors.forename: Laurent
authors.initials: L
authors.lastname: Pays
authors.affiliation: ‖Center for industrial mathematics, University of Bremen, Bibliothek straβe 1, MZH, Room 2060, 28359 Bremen, Germany;
authors.forename: Lena
authors.initials: L
authors.lastname: Hauberg-Lotte
authors.affiliation: ‖Center for industrial mathematics, University of Bremen, Bibliothek straβe 1, MZH, Room 2060, 28359 Bremen, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Maass
authors.affiliation: **Steinbeis Innovation Center SCiLS Research, Fahrenheitstr. 1, 28359 Bremen, Germany;
authors.forename: Jan H
authors.initials: JH
authors.lastname: Kobarg
authors.affiliation: ‡‡Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut.
authors.forename: Firas
authors.initials: F
authors.lastname: Kobeissy
authors.affiliation: From the ‡Univ. Lille, Inserm, U-1192 - Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, F-59000 Lille, France;
authors.forename: Céline
authors.initials: C
authors.lastname: Mériaux
authors.affiliation: From the ‡Univ. Lille, Inserm, U-1192 - Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, F-59000 Lille, France;
authors.forename: Maxence
authors.initials: M
authors.lastname: Wisztorski
authors.affiliation: §Institute of Neurobiology, Slovak Academy of Sciences, Center of Excellence for Brain Research, Soltesovej 4-6 Kosice, Slovakia;
authors.forename: Lucia
authors.initials: L
authors.lastname: Slovinska
authors.affiliation: §Institute of Neurobiology, Slovak Academy of Sciences, Center of Excellence for Brain Research, Soltesovej 4-6 Kosice, Slovakia;
authors.forename: Juraj
authors.initials: J
authors.lastname: Blasko
authors.affiliation: §§Department of Anatomy, Histology and Physiology, University of Veterinary Medicine and Pharmacy in Kosice, Komenskeho 73, 041 81 Kosice, Slovakia.
authors.forename: Viera
authors.initials: V
authors.lastname: Cigankova
authors.affiliation: From the ‡Univ. Lille, Inserm, U-1192 - Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, F-59000 Lille, France;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fournier
authors.affiliation: From the ‡Univ. Lille, Inserm, U-1192 - Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, F-59000 Lille, France; **Steinbeis Innovation Center SCiLS Research, Fahrenheitstr. 1, 28359 Bremen, Germany;
authors.forename: Michel
authors.identifier: 0000-0003-4318-0817
authors.initials: M
authors.lastname: Salzet
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D040081:Protein Array Analysis; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines