Cerebral ischemic preconditioning protects neurons from apoptosis via decoy receptors

Abstract

Cerebral ischemia induces cytokine secretion resulting in neuronal damage. One such factor is TNF related apoptotic‐inducing ligand (TRAIL). Ischemic preconditioning (IPC) is a phenomenon where brief episodes of ischemia protect the brain from lethal injury. Decoy receptors, a subset of TRAIL receptors containing ligand binding but no signaling capacity, act as a sink to compete for TRAIL inhibiting apoptosis. We hypothesize that IPC protects neurons against TRAIL‐induced neuronal death by increasing expression of decoy receptors. Neurons were isolated from 1‐day‐old rat pubs and subjected to TRAIL‐induced apoptosis with and without IPC. IPC was induced by oxygen‐glucose deprivation for 20 min one day prior to TRAIL treatment. Cell death and apoptotic protein expression was assessed 24 h after TRAIL treatment. Trypan blue inclusion assay showed that IPC protects neuron form TRAIL‐induced death. Western blot analysis showed IPC increased expression of decoy receptors as well as decreased pro‐apoptotic (cleaved caspase‐3, CAD and Bad) and increased anti‐apoptotic (Bcl‐2) protein expression 24 h after TRAIL treatment. These data suggest that the protective effects of IPC may result from altered expression of decoy receptors that efficiently compete to limit pro‐apoptotic signaling in neurons. Thus, decoy receptors represent a novel target to limit stroke‐induced neuronal injury.