DFMO reduces cortical infarct volume after middle cerebral artery occlusion in the rat.
Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is induced in ischemic tissue and may mediate vasogenic edema and delayed neuronal death. We determined the effects of alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC, on infarct size and ODC activity in a rat model of transient focal ischemia. DFMO blocked the ischemia-induced increase in ODC and significantly reduced infarct volumes by 57-45%, depending upon the treatment regimen. These studies suggest that polyamine metabolism plays a role in the development of cerebral infarction after focal ischemia and that DFMO may be useful in limiting injury after a stroke.
Muszynski
C A
CA
Department of Otorhinolaryngology, Baylor College of Medicine 77030.
Robertson
C S
CS
Goodman
J C
JC
Henley
C M
CM
D000818:Animals; D002536:Cerebral Arteries; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003250:Constriction; D000518:Eflornithine / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000150:complications*; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D010296:Parietal Lobe / Q000201:enzymology / Q000473:pathology; D051381:Rats
D065108:Ornithine Decarboxylase Inhibitors; D009955:Ornithine Decarboxylase; D000518:Eflornithine