University of Louisville
Naikui Liu

Role of cPLA2 in Mediating Spinal Cord Secondary Injury

There are two mechanisms of damage to the spinal cord after acute spinal cord injury (SCI): the primary mechanical injury and a secondary injury mediated by multiple injury processes including inflammation, free radical-induced cell death and glutamate excitotoxicity. Growing evidence suggests that activation and expression of PLA2, a key enzyme responsible for inflammation and cytotoxicity, can be induced by these multiple harmful substances such as inflammatory cytokines, free radicals, and excitatory amino acids. Over-stimulation of PLA2 is thought to be an important event in the inflammation associated with numerous acute and chronic neurological disorders. However, up to date, it is not clear whether PLA2 plays a role following SCI. In this application, we propose a central hypothesis that PLA2 is a converging molecule that mediates multiple pathological pathways during the course of spinal cord secondary injury. Blocking such a converging molecule as PLA2 may represent a novel strategy to block multiple injury pathways associated with spinal cord secondary injury. To test this central hypothesis, we will investigate the temporal profile and spatial changes of cPLA2 activity and expression, its distribution and cellular location in the injured cord after contusive SCI using biochemical, immunohistochemical, and immunofluorescence double-labeling methods. Furthermore, we will explore the effects of inhibiting this enzyme on neuroprotection and functional recovery after acute SCI using arachidonyl trifluromethyl ketone (AACOCF3), a potent specific inhibitor of cPLA2.