title: SCO-spondin derived peptide NX210 induces neuroprotection in vitro and promotes fiber regrowth and functional recovery after spinal cord injury.
abstract: In mammals, the limited regenerating potential of the central nervous system (CNS) in adults contrasts with the plasticity of the embryonic and perinatal periods. SCO (subcommissural organ)-spondin is a protein secreted early by the developing central nervous system, potentially involved in the development of commissural fibers. SCO-spondin stimulates neuronal differentiation and neurite growth in vitro. NX210 oligopeptide was designed from SCO-spondin's specific thrombospondin type 1 repeat (TSR) sequences that support the main neurogenic properties of the molecule. The objective of this work was to assess the neuroprotective and neuroregenerative properties of NX210 in vitro and in vivo for the treatment of spinal cord injury (SCI). In vitro studies were carried out on the B104 neuroblastoma cell line demonstrating neuroprotection by the resistance to oxidative damage using hydrogen peroxide and the measure of cell viability by metabolic activity. In vivo studies were performed in two rat models of SCI: (1) a model of aspiration of dorsal funiculi followed by the insertion of a collagen tube in situ to limit collateral sprouting; white matter regeneration was assessed using neurofilament immunostaining; (2) a rat spinal cord contusion model to assess functional recovery using BBB scale and reflex testing. We demonstrate for the first time that NX210 (a) provides neuroprotection to oxidative stress in the B104 neuroblastoma cells, (b) stimulates axonal regrowth in longitudinally oriented neofibers in the aspiration model of SCI and (c) significantly improves functional recovery in the contusive model of SCI.
authors.affiliation: Image-Guided Clinical Neuroscience and Connectomics, EA7282, Faculté de Médecine, Université d'Auvergne, Clermont-Ferrand, France; Service de Neurochirurgie, Centre Hospitalier et Universitaire de Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Sakka
authors.affiliation: Neuronax, Biopôle Clermont-Limagne, Saint-Beauzire, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Delétage
authors.affiliation: Homéostasie Cellulaire et Pathologies, EA3842, Faculté de Médecine, Limoges, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lalloué
authors.affiliation: Neuronax, Biopôle Clermont-Limagne, Saint-Beauzire, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Duval
authors.affiliation: Image-Guided Clinical Neuroscience and Connectomics, EA7282, Faculté de Médecine, Université d'Auvergne, Clermont-Ferrand, France; Service de Neurochirurgie, Centre Hospitalier et Universitaire de Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Chazal
authors.affiliation: Image-Guided Clinical Neuroscience and Connectomics, EA7282, Faculté de Médecine, Université d'Auvergne, Clermont-Ferrand, France; Service de Neurochirurgie, Centre Hospitalier et Universitaire de Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lemaire
authors.affiliation: Laboratoire GReD/Inserm U 110/CNRS, UMR 629, Faculté de Médecine, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Meiniel
authors.affiliation: Department of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Hubert
authors.initials: H
authors.lastname: Monnerie
authors.affiliation: Neuronax, Biopôle Clermont-Limagne, Saint-Beauzire, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gobron
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry*; D045744:Cell Line, Tumor; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C108402:SCO-spondin; D006861:Hydrogen Peroxide