Grant: Proof of Principle Program - Phase I

Brain swelling is a gradual process that becomes life-threatening within days of injury, and is caused by sodium chloride drawing water into the nerve cells. This swelling-known as cytotoxic edema-eventually kills brain cells. Severe brain swelling is life threatening because the skull, which normally protects the brain, also limits its ability to expand. With increasing pressure and nowhere to go, the parts of the brain that control breathing can be crushed. At present, there are very limited treatment options and when these fail, an operation is performed in which a portion of the skull is removed and the brain is allowed to swell outside of the skull. Although extreme, it can save the patient's life, but the procedure is not always effective nor without complications. There is an urgent need for new treatments. The current project will identify blockers of a newly identified protein that underlies nerve cell swelling and that leads to cell death and brain swelling. By turning off this single protein the accumulation of fluid into nerve cells will be blocked and nerve cells no longer die.