INTRACEREBRAL HUMAN MICRODIALYSIS - IN-VIVO STUDY OF AN ACUTE FOCAL ISCHEMIC MODEL OF THE HUMAN BRAIN

Background and Purpose In vivo microdialysis was introduced in 1982 as a technique to study cerebral neurochemistry in awake, freely moving animals. In small animals, bilateral carotid occlusion produces a 7- t o 10-fold increase in extracellular glutamate concentrations. This rap idly falls with reperfusion. Increase in extracellular glutamate is cu rrently believed to be a major factor in initiating neuronal injury. G lutamate antagonists are currently undergoing clinical trials in acute stroke. Human data on the extracellular levels of glutamate and other amino acids in the normal or ischemic brain are limited. In this comm unication we wish to report the extracellular concentrations of glutam ate, serine, glutamine, glycine, taurine, alanine, and gamma-aminobuty ric acid, as monitored by in vivo microdialysis, in the simulated isch emic model of the temporal lobe of the human brain. Methods Intracereb ral microdialysis was carried out in five patients who underwent resec tion of the temporal lobe for intractable epilepsy. Surgical excision leads to an acute (from partial to total, ie, from incomplete to compl ete) ischemic state of the resected brain. This was our model to study the changes in human extracellular fluid during acute focal ischemic conditions. Results Extracellular glutamate concentrations were 15 to 30 mu mol/L in the preischemic samples. This increased to 380.69+/-42. 14 mu mol/L with partial (incomplete) ischemia and reached a peak of 1 781.67+/-292.34 mu mol/L (>100-fold) with total isolation of the tempo ral pole (complete ischemia). The levels fell to 394.52+/-72.93 mu mol /L 20 minutes after resection, Similar trends were observed with the o nset of ischemia in the dialysate levels of serine, glutamine, glycine , alanine, taurine, and gamma-aminobutyric acid. Conclusions Our resul ts show that there is a significant increase in extracellular glutamat e and other neurotransmitters with ischemia in the temporal lobe model of the human brain. This increase is of a higher magnitude than that in small animals.