Each year, approximately 10,000 Irish people have a stroke and around 2,000 die – more deaths than breast cancer, prostate cancer and bowel cancer combined. An estimated 30,000 people in the community are living with disabilities as a result of a stroke. This makes stroke the third biggest cause of death in Ireland and the biggest cause of acquired disability. In hypoxia, one component of stroke, nerve cells initiate responses which protect against damage and encourage survival. However more severe hypoxia activates other pathways leading to irreversible brain tissue damage. No novel therapeutics have come to the clinic in the last 25 years to combat this damage to the brain. Enzymes and ROS scavengers which can protect neurons during hypoxia are now under investigation in clinical trials. However there is a lack of data concerning their specific effects on brain cell signalling. This project will allow us to gain valuable insight into the cellular action of these putative therapeutics in the brain. We will utilise electrophysiology to investigate the effects of Roxadustat a prolyl hydroxylase inhibitor and Edaravone a ROS scavenger on the recovery of synaptic transmission following 15 min of oxygen and glucose depravation (OGD) – our stroke model. Our hypothesis is that these agents will protect hippocampal neuron during the OGD and allow synaptic transmission to recover more significantly compared to controls.
