Transgenic rats as models for studying the role of ornithine decarboxylase expression in permanent middle cerebral artery occlusion.
OBJECTIVE
Cerebral ischemia causes activation of ornithine decarboxylase (ODC) gene and subsequent accumulation of putrescine, which might either directly or indirectly affect the outcome of cerebral infarct. We developed a transgenic rat overexpressing human ODC, which was used to explore the effect of abnormally high putrescine concentration in the brain on the infarct volume after permanent middle cerebral artery (MCA) occlusion.


METHODS
The transgenic rats were produced by the pronuclear injection technique with the use of cloned human ODC gene. The right MCA was permanently occluded through craniotomy. ODC activity and polyamines were assayed in the infarcted and contralateral hemispheres. MRI was used to quantify T2 relaxation time, apparent diffusion constant (ADC), and infarct volume, which was also determined by 2,3,5-triphenyltetrazolium chloride.


RESULTS
Permanent MCA occlusion resulted in extensive activation of ODC, which was approximately sevenfold greater than in syngenic animals at 20 hours after occlusion. Consequently, putrescine increased from approximately 10 and 230 pmol/mg to 160 and 410 pmol/mg in the infarcted hemisphere of syngenic and transgenic animals, respectively, but all the other polyamines were unchanged. This high putrescine in the transgenic rats did not influence infarct size evolution, as determined by MRI, T2, ADC, or the infarct volume by 2,3,5-triphenyltetrazolium chloride at 48 hours.


CONCLUSIONS
Data from the ODC transgenic rat model show that the development of brain infarct after permanent MCA occlusion was not influenced by extensive levels of putrescine, indicating that this endogenous amine is not involved in maturation and spread of stroke lesion in vivo. Thus, it seems that ODC activation reflects an endogenous adaptation of neural cells to a noxious stimulus that does not directly influence lesion development.
Lukkarinen
J
J
Nuclear Magnetic Resonance Research Group, University of Kuopio, Finland.
Gröhn
O H
OH
Sinervirta
R
R
Järvinen
A
A
Kauppinen
R A
RA
Jänne
J
J
Alhonen
L I
LI
D000818:Animals; D030801:Animals, Genetically Modified; D001157:Arterial Occlusive Diseases / Q000175:diagnosis / Q000201:enzymology*; D002545:Brain Ischemia / Q000175:diagnosis / Q000201:enzymology*; D016923:Cell Death; D004195:Disease Models, Animal; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D011073:Polyamines; D009955:Ornithine Decarboxylase; D011700:Putrescine