Analysis of a new neuroimmune stress pathway in spinal cord injury (R-3493)

Pre-operative stress has become an inevitable part of patients life. The outcome of stress exposure depends partly on the duration: acute stress exposure leads to immune activation, whereas chronic stress is immunosuppressive. Thermal stress in humans affects catecholamine and cortisol levels, major mediators of the two canonical pathways in a stress response. Increasing evidence points to a third stress pathway mediated by the immune system which has been characterized only in the peripheral nervous system so far. Mast cells (MC) play a key role in this pathway since they are activated by neuropeptides secreted in response to stress, and activation of these MC leads to a release of pro-inflammatory mediators. Therefore, the role of the new stress pathway will be investigated in comparison with the two classical stress pathways. SYSTEMIC effects of acute pre-operative hypothermic stress will be evaluated in a model of spinal cord injury (SCI) in vivo. The LOCAL effects of the three mediators will be studied using neurite outgrowth and neuronal survival assays in vitro. These experiments will elucidate the impact of the neuropeptide/MC pathway and the two classical stress pathways on neurodegeneration. This opens doors to new pharmacological strategies against stress-induced neurodegeneration and mortality after SCI.

Keywords:SPINAL CORD INJURY

Disciplines:Basic sciences, Clinical sciences, Paramedical sciences, Translational sciences