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 journalArticle

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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  • Cite this

    Repici, M., Chen, X., Morel, M-P., Doulazmi, M., Sclip, A., Cannaya, V., Veglianese, P., Kraftsik, R., Mariani, J., Borsello, T., & Dusart, I. (2012). Specific inhibition of the JNK pathway promotes locomotor recovery and neuroprotection after mouse spinal cord injury. Neurobiology of Disease, 46(3), 710-721. https://doi.org/10.1016/j.nbd.2012.03.014