Ornithine decarboxylase activity in in vivo and in vitro models of cerebral ischemia.
Ornithine decarboxylase (ODC) is considered the rate-limiting enzyme in polyamine biosynthesis, and an increase in putrescine after central nervous system (CNS) injury appears to be involved in neuronal death. Cerebral ischemia and reperfusion trigger an active series of metabolic events, which eventually lead to neuronal death. In the present study, ODC activity was evaluated following transient focal cerebral ischemia and reperfusion in rat. The middle cerebral artery (MCA) was occluded for 2 h in male rats with an intraluminal suture technique. Animals were sacrificed between 3 and 48 h of reperfusion following MCA occlusion, and ODC activity was assayed in cortex and striatum. ODC activity was also estimated in an in vitro ischemia model using primary rat cortical neuron cultures, at 6-24 h reoxygenation following 1 h oxygen-glucose deprivation (OGD). In cortex, following ischemia, ODC activity was increased at 3 h (P < .05), reached peak levels by 6-9 h (P < .001) and returned to sham levels by 48 h reperfusion. In striatum the ODC activity followed a similar time course, but returned to basal levels by 24 h. This suggests that ODC activity is upregulated in rat CNS following transient focal ischemia and its time course of activation is region specific. In vitro, ODC activity showed a significant rise only at 24 h reoxygenation following ischemic insult. The release of lactate dehydrogenase (LDH), an indicator for cell damage, was also significantly elevated after OGD. 0.25 mM alpha-difluoromethylornithine (DFMO) inhibited ischemia-induced ODC activity, whereas a 10-mM dose of DFMO appears to provide some neuroprotection by suppressing both ODC activity and LDH release in neuronal cultures, suggesting the involvement of polyamines in the development of neuronal cell death.
Babu
G Nagesh
GN
Department of Neurology, SGPG Institute of Medical Sciences, Lucknow, UP, 226014, India. gnageshbabu@yahoo.com
Sailor
Kurt A
KA
Beck
Joseph
J
Sun
Dandan
D
Dempsey
Robert J
RJ
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR
D009955:Ornithine Decarboxylase; D010100:Oxygen