ORNITHINE DECARBOXYLASE ACTIVITY IN CEREBRAL POSTISCHEMIC REPERFUSIONDAMAGE - EFFECT OF METHIONINE SULFOXIMINE

Excessive activation of glutamate receptors via the N-methyl-D-asparta te (NMDA) subtype appears to play a role in the sequence of cellular e vents which lead to irreversible ischemic damage to neurons. Furthermo re, NMDA receptor activation induces a stimulation of ornithine decarb oxylase (ODC), the rate-limiting enzyme for polyamine (PA) biosynthesi s. In order to better understand the role of PA we have measured ODC a ctivity and the effect of methionine sulfoximine (MSG), a molecule abl e to stimulate ODC, on a model of transient cerebral ischemia. There w as a significant increase in ODC activity in the rat cerebral cortex d uring post-ischemic reperfusion. The treatment with MSO induced a sign ificant decrease in cerebral glutamine synthetase activity accompained by a marked increase in ODC activity. In MSO-pretreated rats there wa s a significant decrease in the survival rate when compared to untreat ed ischemic rats.