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

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

Format: Article
Diterbitkan: Elsevier 2012-06-01

Deskripsi

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 6 h 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.