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- to 10-fold increase in extracellular glutamate concentrations. This rapidly falls with reperfusion. Increase in extracellular glutamate is currently believed to be a major factor in initiating neuronal injury. Glutamate 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 communication we wish to report the extracellular concentrations of glutamate, serine, glutamine, glycine, taurine, alanine, and gamma-aminobutyric acid, as monitored by in vivo microdialysis, in the simulated ischemic model of the temporal lobe of the human brain.

METHODS

Intracerebral microdialysis was carried out in five patients who underwent resection of the temporal lobe for intractable epilepsy. Surgical excision leads to an acute (from partial to total, ie, from incomplete to complete) 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 mumol/L in the preischemic samples. This increased to 380.69 +/- 42.14 mumol/L with partial (incomplete) ischemia and reached a peak of 1781.67 +/- 292.34 mumol/L (> 100-fold) with total isolation of the temporal pole (complete ischemia). The levels fell to 394.52 +/- 72.93 mumol/L 20 minutes after resection. Similar trends were observed with the onset of ischemia in the dialysate levels of serine, glutamine, glycine, alanine, taurine, and gamma-aminobutyric acid.

CONCLUSIONS

Our results show that there is a significant increase in extracellular glutamate 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.