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

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.

► JNK inhibitor D-JNKI1 was administered ip 6 h after spinal cord injury in mice.
► JNK inhibition improves locomotor activity evaluated by both footprint and BMS tests.
► JNK inhibition prevents c-jun phosphorylation and caspase-3 cleavage.
► JNK inhibition resulted in neuroprotection and increased sparing white matter.
► D-JNKI1 treated animals presented less erythrocyte extravasation and BBB opening.