THE POLYAMINE SYNTHESIS INHIBITOR ALPHA-DIFLUOROMETHYLORNITHINE IS NEUROPROTECTIVE AGAINST N-METHYL-D-ASPARTATE-INDUCED BRAIN-DAMAGE INVIVO

We examined the ability of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, the rate limiting enzyme for polyamine biosynthesis, to protect the brain of the perinatal rat from N-methyl-D-aspartate (NMDA)-induced brain damage. Treatment of the rat pups with DFMO administered either by i.p. injection (500 mg/kg x 2) or through the milk of the mother (2% solution in mother's drinking water) significantly reduced, by 48 and 62%, respectively, the brain damage produced by intrastriatal NMDA injection. We conclude that activation of polyamine synthesis may mediate part of the neurotoxic action of NMDA.