title: Specific inhibition of the JNK pathway promotes locomotor recovery and neuroprotection after mouse spinal cord injury.
abstract: Limiting the development of secondary damage represents one of the major goals of neuroprotective therapies after spinal cord injury. Here, we demonstrate that specific JNK inhibition via a single intraperitoneal injection of the cell permeable peptide D-JNKI1 6h after lesion improves locomotor recovery assessed by both the footprint and the BMS tests up to 4 months post-injury in mice. JNK inhibition prevents c-jun phosphorylation and caspase-3 cleavage, has neuroprotective effects and results in an increased sparing of white matter at the lesion site. Lastly, D-JNKI1 treated animals show a lower increase of erythrocyte extravasation and blood brain barrier permeability, thus indicating protection of the vascular system. In total, these results clearly point out JNK inhibition as a promising neuroprotective strategy for preventing the evolution of secondary damage after spinal cord injury.
authors.affiliation: UPMC Univ Paris 06, UMR 7102, Paris, France.
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Repici
authors.forename: Xiaoru
authors.initials: X
authors.lastname: Chen
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Morel
authors.forename: Mohamed
authors.initials: M
authors.lastname: Doulazmi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sclip
authors.forename: Vidjeacoumary
authors.initials: V
authors.lastname: Cannaya
authors.forename: Pietro
authors.initials: P
authors.lastname: Veglianese
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kraftsik
authors.forename: Jean
authors.initials: J
authors.lastname: Mariani
authors.forename: Tiziana
authors.initials: T
authors.lastname: Borsello
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dusart
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D006614:Hindlimb / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D009412:Nerve Fibers / Q000502:physiology; D018696:Neuroprotective Agents; D010455:Peptides / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology
chemical_list: D018696:Neuroprotective Agents; D010455:Peptides; D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D012701:Serotonin; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; C478085:D-JNKI-1