Differing effects of alpha-difluoromethylornithine and CGP 40116 on polyamine levels and infarct volume in a rat model of focal cerebral ischaemia.
Focal cerebral ischaemia was induced in rats by occlusion of the left middle cerebral artery. Two days later, infarct volume was determined by magnetic resonance imaging and the concentrations of the polyamines putrescine (PU), spermine and spermidine by HPLC. In control (occluded) animals, PU levels were elevated in infarcted and non-infarcted areas of the left hemisphere. Treatment with the ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine, prevented the ischaemia-induced increase in tissue PU without affecting infarct volume. Conversely, administration of the N-methyl-D-aspartate (NMDA) receptor antagonist CGP 40116 decreased cortical infarction without changing the tissue content of PU. We conclude that there is no direct link between NMDA receptor activation and brain PU, or PU and post-ischaemic tissue damage, and that inhibitors of ODC are not cerebroprotective in this animal model of stroke.
Ciba-Geigy, Pharmaceutical Research Division, Basel, Switzerland.
D
D
Sauer
P
P
Martin
P R
PR
Allegrini
R
R
Bernasconi
H
H
Amacker
G E
GE
Fagg
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000175:diagnosis / Q000473:pathology*; D002544:Cerebral Infarction / Q000175:diagnosis / Q000473:pathology*; D000518:Eflornithine / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D013096:Spermine; D015763:2-Amino-5-phosphonovalerate; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine