Effect of difluoromethylornithine on reperfusion injury after temporary middle cerebral artery occlusion.
Polyamines have been shown to play an important role in the disturbance of the blood-brain barrier (BBB) in a number of pathological states including ischemia. BBB disturbances may be almost completely prevented by treating animals with the ornithine decarboxylase (ODC) inhibitor, alpha-difluoromethylornithine (DFMO). DFMO has been also shown to prevent N-Methyl-D-aspartate (NMDA) toxicity in tissue cultures. It has been suggested that the pathological disturbances in polyamine metabolism observed following cerebral ischemia, particularly the post-ischemic increase in putrescine, may contribute to the ischemic injury that is most evident in the CA1 subfield of the hippocampus. In this study, effects of DFMO in cerebral ischemia and reperfusion were examined. The results showed that inhibition of the polyamine system by DFMO decreased ischemic injury volume and brain tissue water content in a dose-dependent manner, without change in vital signs, including systemic arterial blood pressure, arterial partial oxygen pressure, regional cerebral blood flow and body temperature.
Temiz
Cuneyt
C
Department of Neurosurgery, Celal Bayar University, Faculty of Medicine, Manisa, Turkey. temiz2@tr.net
Dogan
Aclan
A
Baskaya
Mustafa K
MK
Dempsey
Robert J
RJ
D000818:Animals; D001929:Brain Edema / Q000473:pathology / Q000517:prevention & control; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000503:physiopathology; D007427:Intracranial Pressure / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D015427:Reperfusion Injury / Q000517:prevention & control*
D004791:Enzyme Inhibitors; D000518:Eflornithine