Implication of the polyamines in the neurotoxic effects of N-methyl-D-aspartate

N-Methyl-D-aspartate (NMDA) receptor activation selectively releases the polyamines spermine and spermidine from the rat striatum in vivo. The intrastriatal injection of spermine or spermidine is neurotoxic, but this toxicity is not blocked by MK-801 and unlikely to be mediated via the NMDA receptor. The neurotoxic effects of intrastriatally injected NMDA can, however, be reduced by polyamine synthesis inhibition with difluoromethylornithine. Alterations in polyamine metabolism in the ischaemic brain, although perhaps induced by NMDA receptor activation, may contribute to ischaemic cell loss via NMDA-independent mechanisms, possibly related to the diverse effects of polyamines on calcium homoeostasis and channel function.