Specific inhibition of the JNK pathway promotes locomotor recovery and neuroprotection after mouse spinal cord injury

Mariaelena Repici, Xiaoru Chen, Marie-Pierre Morel, Mohamed Doulazmi, Alessandra Sclip, Vidjeacoumary Cannaya, Pietro Veglianese, Rudolf Kraftsik, Jean Mariani, Tiziana Borsello, Isabelle Dusart

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)710-721
Number of pages12
JournalNeurobiology of Disease
Volume46
Issue number3
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Animals
  • Blood Vessels/drug effects
  • Blotting, Western
  • Caspase 3/metabolism
  • Hindlimb/physiology
  • Image Processing, Computer-Assisted
  • Imaging, Three-Dimensional
  • Immunohistochemistry
  • Injections, Intraperitoneal
  • JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors
  • Locomotion/drug effects
  • Male
  • Mice
  • Nerve Fibers/physiology
  • Neuroprotective Agents
  • Peptides/pharmacology
  • Protein Kinase Inhibitors/administration & dosage
  • Proto-Oncogene Proteins c-jun/metabolism
  • Recovery of Function/drug effects
  • Serotonin/physiology
  • Signal Transduction/drug effects
  • Spinal Cord/pathology
  • Spinal Cord Injuries/drug therapy

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