Comparative neurotoxic potential of glutamate, endothelins, and platelet-activating factor in cerebral cortical cultures

The excitatory amino acid glutamate, the peptides endothelin-1 and -3, and the phospholipid platelet-activating factor have been implicated in ischemic injury to the nervous system. To determine if, like glutamate, endothelins and platelet-activating factor are directly toxic to neurons, we examined their effects on lactate dehydrogenase release and trypan blue dye exclusion in rat cerebral cortical cultures. Glutamate (1 mM) increased lactate dehydrogenase release by approximately 75% and reduced the number of cells excluding trypan blue dye by approximately 50%. In contrast, endothelins (0.5 and 100 nM) and platelet-activating factor (0.1 and 10 microM) had no effect on these indices of cell injury. Endothelins and platelet-activating factor appear more likely to act on blood vessels than on neurons or glia as mediators of ischemic injury.