Difluoromethyl ornithine protects against the neurotoxic effects of intrastriatally administered N-methyl-D-aspartate in vivo.

The neurotoxic effects of intrastriatally administered N-methyl-D-aspartate (NMDA) (250 nmol), as measured by reductions in striatal choline acetyl transferase activity and by increased binding of the glial marker [3H]PK 11195 10 days later, were reduced by coinfusion of the irreversible ornithine decarboxylase inhibitor difluoromethylornithine (250 nmol) in the rat. The data suggest a crucial role for the polyamines in NMDA receptor-mediated neurotoxicity.