Glutamate infusion coupled with hypoxia has a neuroprotective effect in the rat

Traumatic brain injury leads to a rise in glutamate, interference with oxygen supply and secondary neuronal death in the region surrounding the primary lesion. In the present experiments we have examined the effect of combining glutamate infusion with hypoxia on both brain metabolism and neuronal death. We have used microdialysis in unanaesthetised rats with a novel dual assay for glucose and lactate to monitor the temporal relation of changes in these metabolites resulting from infusion of 100 mM glutamate alone or combined with a reduction of inspired oxygen to 8%. In a parallel series of experiments we have compared the size of heuronal lesions under the same experimental conditions. We have used MAP2 antibody staining to measure the size of the neuronal lesion. Our results demonstrate that a 30 min glutamate infusion causes an immediate increase in neuronal glucose utilisation and a rise in lactate production. When hypoxia is added during the last 15 min of glutamate infusion there is a small rise in glucose and a large additional increase in lactate. The size of the neuronal lesions produced by infusion of 100 mM glutamate is reduced by the addition of hypoxia. (C) 2002 Elsevier Science B.V. All rights reserved.