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

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MAP Kinase Signaling System
Spinal Cord Injuries
Neuroprotective Agents
Intraperitoneal Injections
Blood-Brain Barrier
Caspase 3
Blood Vessels
Permeability
Erythrocytes
Phosphorylation
Peptides
Wounds and Injuries
Neuroprotection
D-JNKI-1
Therapeutics
White Matter

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

Cite this

Repici, Mariaelena ; Chen, Xiaoru ; Morel, Marie-Pierre ; Doulazmi, Mohamed ; Sclip, Alessandra ; Cannaya, Vidjeacoumary ; Veglianese, Pietro ; Kraftsik, Rudolf ; Mariani, Jean ; Borsello, Tiziana ; Dusart, Isabelle. / Specific inhibition of the JNK pathway promotes locomotor recovery and neuroprotection after mouse spinal cord injury. In: Neurobiology of Disease. 2012 ; Vol. 46, No. 3. pp. 710-721.
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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.",
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author = "Mariaelena Repici and Xiaoru Chen and Marie-Pierre Morel and Mohamed Doulazmi and Alessandra Sclip and Vidjeacoumary Cannaya and Pietro Veglianese and Rudolf Kraftsik and Jean Mariani and Tiziana Borsello and Isabelle Dusart",
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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, vol. 46, no. 3, pp. 710-721. https://doi.org/10.1016/j.nbd.2012.03.014

Specific inhibition of the JNK pathway promotes locomotor recovery and neuroprotection after mouse spinal cord injury. / Repici, Mariaelena; Chen, Xiaoru; Morel, Marie-Pierre; Doulazmi, Mohamed; Sclip, Alessandra; Cannaya, Vidjeacoumary; Veglianese, Pietro; Kraftsik, Rudolf; Mariani, Jean; Borsello, Tiziana; Dusart, Isabelle.

In: Neurobiology of Disease, Vol. 46, No. 3, 06.2012, p. 710-721.

Research output: Contribution to journalArticle

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AU - Sclip, Alessandra

AU - Cannaya, Vidjeacoumary

AU - Veglianese, Pietro

AU - Kraftsik, Rudolf

AU - Mariani, Jean

AU - Borsello, Tiziana

AU - Dusart, Isabelle

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