Neurotoxicity of glutamate at the concentration released upon spinal cord injury

Damage caused by administering glutamate into the spinal cord was character ized histologically. Glutamate destroyed neurons for several hundred microm eters around the administering microdiaIysis fiber. At 24h after treatment, significant (P = 0.036) loss of neurons was observed (75%) relative to con trol (47%) near the fiber when glutamate was administered for 1 h at a conc entration outside the fiber approximating the maximum glutamate released up on spinal cord injury. Significant loss of neurons (P = 0.006, 0.022) was a lso caused by administering a combination of glutamate at about its average concentration released upon injury over the 1 h period of administration i n combination with the maximum aspartate concentration released upon injury . This work provides a direct demonstration that the concentrations of excita tory amino acids released upon spinal cord injury are neurotoxic. The destr uction of neurons by exposure to excitatory amino acids when there is also substantial loss of neurons simply from the presence of the microdialysis f iber may reflect sensitization of neurons to excitotoxicity by stress. (C) 1999 IBRO. Published by Elsevier Science Ltd.