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 language | English |
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Pages (from-to) | 710-721 |
Number of pages | 12 |
Journal | Neurobiology of Disease |
Volume | 46 |
Issue number | 3 |
DOIs | |
Publication status | Published - Jun 2012 |
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