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

doi:10.1016/j.nbd.2012.03.014

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

Neurobiol Dis. 2012 Jun;46(3):710-21. doi: 10.1016/j.nbd.2012.03.014. Epub 2012 Mar 9.

Authors

Mariaelena Repici¹, Xiaoru Chen, Marie-Pierre Morel, Mohamed Doulazmi, Alessandra Sclip, Vidjeacoumary Cannaya, Pietro Veglianese, Rudolf Kraftsik, Jean Mariani, Tiziana Borsello, Isabelle Dusart

Affiliation

¹ UPMC Univ Paris 06, UMR 7102, Paris, France.

PMID: 22426389
DOI: 10.1016/j.nbd.2012.03.014

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Vessels / drug effects
Blood Vessels / physiology
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
Protein Kinase Inhibitors / pharmacology*
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*
Spinal Cord Injuries / enzymology
Spinal Cord Injuries / physiopathology

Substances

Neuroprotective Agents
Peptides
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-jun
Serotonin
JNK Mitogen-Activated Protein Kinases
Caspase 3
D-JNKI-1