Relationship between Excitatory Amino Acid Release and Outcome after Severe Human Head Injury
In previous studies, Katayama and our group have documented a massive increase in excitatory amino acid release following traumatic brain injury, in both rat fluid percussion, and humans [2,5]. To test the hypothesis that the magnitude of this “Excitotoxi
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Relationship between Excitatory Amino Acid Release and Outcome after Severe Human Head Injury S. S. Koura, E. M. R. Doppenberg, A. Marmarou, S. Choi, H. F. Young, and R. Bullock Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, U.S.A.
Summary In previous studies, Katayama and our group have documented a massive increase in excitatory amino acid release following traumatic brain injury, in both rat fluid percussion, and humans [2,5]. To test the hypothesis that the magnitude of this "Excitotoxic Surge" plays a significant role in determining 6-month patient outcome. We have studied 83 consecutive severely head injured patients at the Medical College of Virginia for inclusion into this study. A microdialysis probe was placed within the cortex to continuously measure dialysate excitatory amino acids (Glutamate and Aspartate), along with several other analytes for approximately 5 days after injury. ICP, CPP, and MABP measurements were also time linked with each analyte measurement to create a neurochemical, clinical, and physiological "profile" for each patient. Outcome was determined by follow up using the Glasgow 6Month outcome scale. A very strong correlation existed between the release of the EAA's glutamate and aspartate after TBI (p < 0.0001). Patients with significantly elevated mean glutamate values for the entire monitoring period were most likely to exhibit elevated levels of ICP. The magnitude of glutamate released significantly correlates with 6-month patient outcome (p = 0.0234). When patients were subdivided by the CT diagnosis of lesion type, we found that those patients with contusions displayed the highest overall of EAA's. Keywords: Excitatory amino acid; head injury; outcome.
Introduction The excitatory amino acids (EAA's) glutamate and aspartate have been found to increase up to 6 fold in rats, and 50 fold in human brain dialysate, after TBI [2,3,5]. However, this may be an epiphenomenon since structural amino acids were similarly elevated, in our human studies. There had been no previous direct evidence that this massive release of EAA's has been associated with significantly worse outcome. Developments in the use of clinical microdialysis have made it possible to continuously measure changes in several brain metabolic analytes in the
severely head injured patient [4,7]. We have used these data to test whether increased EAA's correlate with 6-month patient outcome, and whether the lesion type affects the pattern of EAA's release.
Materials and Methods These studies were approved by the Committee for Conduct of Human Research of the Medical College of Virginia and Virginia Commonwealth University. Eighty-three severely head injured patients (GCS ::; 8) were studied. Custom-made, commercially produced microdialysis probes were used, with a molecular weight cutoff of 20 KD and a 10 mm active dialysis surface (CMA 20 Custom probes, CMA Microdialysis, Stockholm, Sweden). The probe was placed intraparenchymally in cortex to
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