Grant: Operating Grant

Our brain works similar to an automobile: to function it requires a continuous supply of energy. Instead of using gasoline our brain uses glucose and oxygen. Both are carried to the brain through the blood. When the large energy demand of the brain is not completely satisfied due to a decreased or completely interrupted flow of blood, a pathological condition known as brain ischemia or stroke occurs. A few minutes after the occurrence of a stroke, a 'serial killer' comes out the cells. This 'serial killer' is named glutamate. Glutamate can cause death or permanent damage if no medical intervention is performed immediately. There is currently no treatment that can stop the 'serial killer'. According to statistical data, brain ischemia represents the third highest cause of death in industrialized countries. The high costs of medical care required by surviving individuals, from whom a large percentage are permanently disabled, is a major cause of economic burden. The ultimate goal of this research proposal is to better understand how a small molecule, named N-acetyl-aspartyl-glutamate (NAAG), that already exists in huge quantities in the brain may be used to stop the 'serial killer'. It may protect the brain in a situation when the blood supply is not sufficient or is interrupted, even for a few minutes. We (our laboratory and other labs around the world) have identified two receptors in the brain on which this small molecule NAAG works. A receptor is a kind of 'door' that allows communication between the inside and the outside of the cells. Too much glutamate is thought to be the cause of cell death. There are billions of cells in the brain and they all have a crucial role in maintaining good functioning of the brain. My research aims to prevent this terrible disease by arresting the 'serial killer' before it commits its crime.