Extracellular concentrations of glutamate and aspartate in the injured brain measured by microdialysis

Introduction: Excitatory amino acids, especially glutamate (GLU) and aspartate (ASP), have been implicated in the pathogenesis of damage to the brain after trauma. This mechanism of injury has been extensively studied in experimental preparations, but clinical data is limited. The purpose of this study was to examine the relationship between the extracellular concentrations of GLU and ASP, measured with intracerebral microdialysis, to outcome after severe traumatic brain injury. Methods: A microdialysis probe was implanted into brain tissue of 79 patients with severe head injury. The probe was perfused at 2 μl/min with sterile saline. The concentrations of GLU and ASP were measured in serial 30 minute collections of microdialysate by HPLC with UV absorbance detection after pre-column phenylisocyanate derivatization. The concentrations of GLU and ASP were related to neurological outcome, type of injury, severity of injury and to other physiological data that was collected, including local brain tissue pO₂ (PbtO₂) and local CBF measured by the thermal diffusion technique (TD-CBF). Results: The median dialysate GLU concentration for all 79 patients was 7.9 μM (interquartile range 3.7; 20 μM). The median dialysate ASP concentation was 2.6 μM (1.2; 5.3 μM). The individual GLU and ASP values obtained during the entire monitoring period were averaged for each patient. These average values for dialysate GLU and ASP were closely related to outcome and to type of injury. Patients who died had significantly higher values than patients who survived (p<.001 and p=.004, for GLU and ASP, respectively). The highest values were found in patients with gunshot wounds, followed by patients with evacuated and unevacuated mass lesions. Patients with diffuse injuries had the lowest values of GLU and ASP. The dialysate concentrations of GLU and ASP were also closely related to the other physiological parameters that were measured, and sharply increased with decreasing TD-CBF and with depletion of the energy substrates, oxygen (measured by PbtO₂) and glucose (also measured in the dialysate). Conclusions: Excitatory amino acids are present in elevated concentrations in human traumatic brain injury, and are strongly related to the severity and type of brain injury, in particular, GLU and ASP were found in very high concentrations in patients with fatal brain injury.