Effects of MDL 72527, a specific inhibitor of polyamine oxidase, on brain edema, ischemic injury volume, and tissue polyamine levels in rats after temporary middle cerebral artery occlusion

The possible effects of the polyamine interconversion pathway on tissue pol yamine levels, brain edema formation, and ischemic injury volume were studi ed by using a selective irreversible inhibitor, MDL 72527, of the interconv ersion pathway enzyme, polyamine oxidase. In an intraluminal suture occlusi on model of middle cerebral artery in spontaneously hypertensive rats, 100 mg/kg MDL 72527 changed the brain edema formation from 85.7 +/- 0.3 to 84.5 +/- 0.9% in cortex (p < 0.05) and from 79.9 +/- 1.7 to 78.4 +/- 2.0% in su bcortex (difference not significant). Ischemic injury volume was reduced by 22% in the cortex (p < 0.05) and 17% in the subcortex (p < 0.05) after inh ibition of polyamine oxidase by MDL 72527, There was an increase in tissue putrescine levels together with a decrease in spermine and spermidine level s at the ischemic site compared with the nonischemic site after ischemia-re perfusion injury. The increase in putrescine levels at the ischemic cortica l and subcortical region was reduced by a mean of 45% with MDL 72527 treatm ent. These results suggest that the polyamine interconversion pathway has a n important role in the postischemic increase in putrescine revels and that blocking of this pathway can be neuroprotective against neuronal cell dama ge after temporary focal cerebral ischemia.