Acute brain diseases like stroke and ischemia (as seen in cardiac arrest) as well as chronic degenerative brain disorders like epilepsy, Alzheimer's disease and Huntington's disease have immense consequences both socioeconomically and individually. It has been suggested that these diseases are linked to abnormal extracellular concentrations of the excitatory neurotransmitter glutamate in the brain. It is of vital importance to establish whether this is true or not to pave the way for pharmaceutical research aimed at rescuing brain cells at risk of degeneration. Inactivation of glutamate is achieved by uptake into nerve cells or glia. The project will use molecular biological techniques (gene targeting) to develop mice without neuronal or glial uptake mechanisms to study the importance of such uptake mechanisms for the survival of nerve cells in animal models of stroke, epilepsy and chronic neurodegeneration.