Neurotoxicity of glutamate at the concentration released upon spinal cord injury

Damage caused by administering glutamate into the spinal cord was characterized histologically. Glutamate destroyed neurons for several hundred micrometers around the administering microdialysis fiber. At 24 h after treatment, significant (P = 0.036) loss of neurons was observed (75%) relative to control (47%) near the fiber when glutamate was administered for 1 h at a concentration outside the fiber approximating the maximum glutamate released upon spinal cord injury. Significant loss of neurons (P = 0.006, 0.022) was also caused by administering a combination of glutamate at about its average concentration released upon injury over the 1 h period of administration in combination with the maximum aspartate concentration released upon injury. This work provides a direct demonstration that the concentrations of excitatory amino acids released upon spinal cord injury are neurotoxic. The destruction of neurons by exposure to excitatory amino acids when there is also substantial loss of neurons simply from the presence of the microdialysis fiber may reflect sensitization of neurons to excitotoxicity by stress.