| Abstract No.: | A-C1079 |
| Country: | Canada |
| | |
| Title: | MAPKAP-K2 CONTROLS INFLAMMATION AND SECONDARY DAMAGE IN SPINAL CORD INJURY |
| | |
| Authors/Affiliations: | 1 Nader Ghasemlou*; 1 Ruben Lopez-Vales; 1 Claude Lachance; 1 Danuta Radzioch; 1 Samuel David;
1 McGill University, Montreal, QC, Canada
|
| | |
| Content: | A hallmark of spinal cord injury (SCI) pathology is the influx of immune cells to the site of injury. These cells (neutrophils and macrophages) produce various mediators of inflammation that can damage healthy tissue (secondary damage). Reducing secondary damage is thought to lead to improved functional outcome after injury.
Objective: The aim of this work was to identify key molecules involved in macrophage activation that contribute to secondary damage after SCI.
Materials and Methods: We carried out an Affymetrix GeneChip screen of the contused spinal cord at the peak of macrophage activation. Based on this analysis, we identified MAPK-activated protein kinase 2 (MK2) as a gene of interest. The role of this gene was assessed after a moderate contusion injury using MK2 knockout (KO) and wildtype (WT) mice.
Results: GeneChip analysis revealed a significant increase in MK2 expression at the peak of macrophage activation in injured spinal cord tissue compared to naïve.. Furthermore, the active form of MK2, phospho-MK2, was highest at 7 days after injury while total MK2 protein also peaked at day 7 and remained elevated until day 28. Locomotor recovery analyzed using the 9-point BMS scale showed significantly better locomotor function in KO mice from day 10 onwards as compared to WT. Histological analysis of spinal cords at 28 days revealed significant reduction in motoneuron and myelin loss in MK2 null mice. There was also increased serotonergic innervation caudal to the injury in the null mice. Immunofluorescence staining showed that neutrophils and macrophages expressed phospho-MK2 after injury. Twelve hours after SCI, the levels of 20 cytokines and chemokines were found to be significantly reduced or abrogated in the MK2 null mice. This was also accompanied by diminished levels of phospho-Hsp27, a downstream effector of MK2 function.
Conclusion: This work suggests an important role for MK2 in the inflammatory response initiated after spinal cord injury. MK2 appears to be a key molecule controlling the activation state of immune cells after injury, and may serve as a useful target for therapeutic intervention after SCI.
|
| | |
| Back |
|
