Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
3069529 | Neurobiology of Disease | 2012 | 12 Pages |
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.