About 40% of central nervous system synapses use glutamate as the neurotransmitter. Over-stimulation of glutamate receptors produces neuronal injury or death by excitotoxicity, which is closely associated with neurochemical and neuropathological changes involved in acute neural trauma (stroke, spinal cord trauma, and head injury) and neurodegenerative diseases such as Alzheimer disease, Parkinson disease , Huntington disease, amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease, Guam-type amyotrophic lateral sclerosis/Parkinson dementia (ALS/PDC), and multiple sclerosis. In the past decade, our understanding of the biochemistry, molecular biology, and neuropathology of the glutamate transporters and receptors has exploded. It is becoming increasingly evident that molecular mechanisms, which govern the transfer of the death signal from the neural cell surface to the nucleus, depend on lipid mediators and on cross talk among excitotoxicity, oxidative stress, and...

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