GLUTAMATE IN NEUROLOGIC-DISEASES

Excitotoxicity has been implicated as a mechanism of neuronal death in acute and chronic neurologic diseases. Cerebral ischemia, head and sp inal cord injury, and prolonged seizure activity are associated with e xcessive release of glutamate into the extracellular space and subsequ ent neurotoxicity. Accumulating evidence suggests that impairment of i ntracellular energy metabolism increases neuronal vulnerability to glu tamate which, even when present at physiologic concentrations, can dam age neurons. This mechanism of slow excitotoxicity may be involved in neuronal death in chronic neurodegenerative diseases such as the mitoc hondrial encephalomyopathies, Huntington's disease, spinocerebellar de generation syndromes, and motor neuron diseases. If so, glutamate anta gonists in combination with agents that selectively inhibit the multip le steps downstream of the excitotoxic cascade or help improve intrace llular energy metabolism may slow the neurodegenerative process and of fer a therapeutic approach to treat these disorders.