Changes in amino acid concentrations over time and space around an impact injury and their diffusion through the rat spinal cord

Release of amino acids, particularly the neurotoxin glutamate, in and around the site of an experimental spinal cord injury was characterized over time by microdialysis. Increases in amino acid concentrations caused by injury decline steeply and then slowly over distance from the impact area, becoming undetectable beyond about 5 mm from the injury epicenter. Diffusion profiles determined in the cord by administering amino acids through one microdialysis fiber and sampling them in a parallel fiber declined steeply with distance. Distant increases coincided temporally with those in the injury epicenter. We conclude that-elevated amino acids more than about 1 mm into the periimpact zone are predominantly released in that region rather than diffusing into it from the trauma epicenter. In the outer areas of lesion development, glutamate does not appear to reach concentrations ordinarily toxic, and elevated concentrations do not persist nearly as long as the therapeutic window of NBQX in any part of the lesion. Therefore, the mechanisms whereby excitatory amino acid antagonists reduce the dimensions of injury lesions are unclear. However, sensitization of neurons following impact injury could be important in amino acid neurotoxicity. (C) 1999 Academic Press.