scholarly journals Ornithine Decarboxylase Activity and Putrescine Levels in Reversible Cerebral Ischemia of Mongolian Gerbils: Effect of Barbiturate

1990 ◽  
Vol 10 (2) ◽  
pp. 236-242 ◽  
Author(s):  
Wulf Paschen ◽  
Joachim Hallmayer ◽  
Günter Mies ◽  
Gabriele Röhn
Keyword(s):  
Cerebral Cortex ◽  
Cerebral Ischemia ◽  
Ornithine Decarboxylase ◽  
Cell Damage ◽  
Fold Increase ◽  
Decarboxylase Activity ◽  
Mongolian Gerbils ◽  
Tissue Samples ◽  
Neuronal Necrosis ◽  
Tissue Sections

Reversible cerebral ischemia was produced in anesthetized Mongolian gerbils by occluding both common carotid arteries. After 5 min of ischemia, brains were recirculated for 8 or 24 h. Treated animals received a single intraperitoneal injection of pentobarbitol (50 mg/kg) immediately after the anuerysm clips were removed. At the end of the experiments, animals were reanesthetized and their brains frozen in situ. Tissue samples were taken from the cerebral cortex, lateral striatum, CA1 subfield of the hippocampus, thalamus, and cerebellum for measuring ornithine decarboxylase (ODC) activity and putrescine levels. In addition, 20-μm-thick coronal tissue sections were taken from the level of the striatum and stained with hematoxylin/eosin for evaluating the extent of ischemic neuronal necrosis in the lateral striatum. In control animals ODC activity and putrescine levels amounted, respectively, to 0.32 ± 0.03 nmol/g/h and 10.2 ±0.5 nmol/g in the cerebral cortex; 0.34 ± 0.02 nmol/g/h and 12.8 ± 0.5 nmol/g in the lateral striatum; 0.58 ± 0.05 nmol/g/h and 10.5 ± 0.7 nmol/g in the hippocampal CA1 subfield; 0.35 ± 0.01 nmol/g/h and 9.8 ± 0.4 nmol/g in the thalamus; and 0.25 ± 0.01 nmol/g/h and 8.3 ± 0.6 nmol/g in the cerebellum. After 5 min cerebral ischemia and 8 h recirculation, a significant 7- to 16-fold increase in ODC activity was observed in all forebrain structures studied. Following 24 h recirculation, ODC activity normalized in the cortex, striatum, and thalamus but was still significantly above control values in the hippocampal CA1 subfield. In the cerebellum ODC activity did not change significantly. Putrescine levels were significantly increased in all forebrain structures after 8 h (two- to threefold) and even more after 24 h recirculation (up to fivefold). In barbiturate-treated animals, ODC activity was not significantly changed in relation to untreated ones. There was, however, a trend to higher activity in the cerebral cortex, lateral striatum, and hippocampal CA1 subfield. Barbiturate did not produce a significant effect on postischemic putrescine levels except in the CA1 subfield. Here the putrescine content of treated animals was significantly below that found in untreated ones. In the lateral striatum, severe cell damage (>90% of neurons were necrotic) was observed in 5 of 12 untreated animals but in none of the barbiturate-treated ones (<10% of neurons necrotic). In animals with severe cell necrosis in the lateral striatum, putrescine levels amounted to 70.9 ± 3.4 nmol/g but to only 32.0 ± 2.9 nmol/g in animals in which <10% of neurons were affected (p ⩽ 0.001).

scholarly journals Ornithine Decarboxylase Activity and Immunohistochemical Location in Postischemic Brain

1988 ◽  
Vol 8 (6) ◽  
pp. 843-847 ◽  
Author(s):  
Robert J. Dempsey ◽  
Bruce E. Maley ◽  
David Cowen ◽  
Jack W. Olson
Keyword(s):  
Cerebral Ischemia ◽  
Ornithine Decarboxylase ◽  
Cortical Neurons ◽  
Vasogenic Edema ◽  
Cerebral Injury ◽  
Decarboxylase Activity ◽  
Mongolian Gerbils ◽  
Edema Formation ◽  
Ornithine Decarboxylase Activity ◽  
Bilateral Carotid

Ornithine decarboxylase, rate-limiting in polyamine formation, has been found to be necessary for the development of vasogenic edema after cryogenic cerebral injury and is postulated to be of importance in late ischemic brain edema formation. Ornithine decarboxylase activity and accompanying edema was studied after transient cerebral ischemia in Mongolian gerbils. Bilateral carotid artery occlusion was utilized to produce dense forebrain ischemia. After 4 h of reperfusion a significant elevation in ornithine decarboxylase activity was present (72.5 ± 24.7 vs 8.5 ± 2 pmoles/mg protein/h, p < 0.05). Immunohistochemical localization of ornithine decarboxylase indicated its presence in cortical neurons of ischemic gerbils. This was typically located in the perinuclear cytoplasm and extended into proximal dendrites. Nonischemic animals did not contain ornithine decarboxylase immunoreactivity. These studies show the presence and location of ornithine decarboxylase in cerebral tissue sUbjected to transient ischemia. The increase in this marker of polyamine activity paralleled previous studies in this model of cerebral edema formation and reperfusion deficit in blood flow and evoked potential, suggesting that ornithine decarboxylase is a marker for and may be associated with those late metabolic events leading to progressive functional deterioration after incomplete cerebral ischemia.

Genotoxicity and Cell Proliferative Activity of 3-Chloro-4-(Dichloromethyl)-5-Hydroxy-2(5H)-Furanone [MX] in Rat Glandular Stomach

1992 ◽  
Vol 25 (11) ◽  
pp. 341-345 ◽  
Author(s):  
C. Furihata ◽  
M. Yamashita ◽  
N. Kinae ◽  
T. Matsushima
Keyword(s):  
Cell Proliferation ◽  
Body Weight ◽  
Dna Synthesis ◽  
Ornithine Decarboxylase ◽  
Tap Water ◽  
Fold Increase ◽  
Single Strand ◽  
Glandular Stomach ◽  
Decarboxylase Activity ◽  
Pyloric Mucosa

MX is a strong direct acting mutagen on Salmonella typhimurium TA100 and is present in chlorinated tap water which contains organic compounds. MX was administered orally to 7-week-old male F344 rats, and its geno-toxicity in the pyloric mucosa of stomach was examined by analysis of DNA single strand scissions by the alkaline elution method. The effect of MX on cell proliferation was examined by assays of the inductions of replicative DNA synthesis and ornithine decarboxylase. MX at closes of 20-48 mg/kg body weight induced DNA single strand scissions dose-dependently (p&lt;0.02) in the pyloric mucosa of the stomach 2 h after its administration. Moreover at doses of 10-60 mg/kg body weight, it induced up to 21-fold increase in replicative DNA synthesis (p&lt;0.01) 16 h after its administration. At doses of 10-60 mg/kg body weight, it induced up to 100-fold increase in ornithine decarboxylase activity with a maximum 16 h after its administration. These results suggest that MX is genotoxic and induces cell proliferation in the glandular stomach of rats.

scholarly journals Transgenic mice expressing the human ornithine decarboxylase gene under the control of mouse metallothionein I promoter

1996 ◽  
Vol 314 (2) ◽  
pp. 405-408 ◽  
Author(s):  
Leena ALHONEN ◽  
Sami HEIKKINEN ◽  
Riitta SINERVIRTA ◽  
Maria HALMEKYTÖ ◽  
Pekka ALAKUIJALA ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Ornithine Decarboxylase ◽  
Mammalian Cells ◽  
Fold Increase ◽  
Transgenic Animals ◽  
Decarboxylase Activity ◽  
Transgenic Mouse Line ◽  
Regulatory Machinery ◽  
Dividing Cells ◽  
Very High

We have generated a transgenic mouse line harbouring the human ornithine decarboxylase gene under the control of mouse metallothionein I promoter. Even in the absence of an exposure to heavy metals, ornithine decarboxylase was over-expressed in heart, testis, brain, and especially in liver, of the transgenic animals. An exposure of the transgenic mice to zinc further enhanced the enzyme activity to a level which in liver represented up to 8000-fold increase in comparison with non-transgenic animals. The striking stimulation of liver ornithine decarboxylase activity upon treatment of the transgenic mice with zinc was accompanied by a nearly 150-fold increase in the hepatic putrescine content as compared with similarly treated non-transgenic animals. Even though the liver putrescine concentration reached that of spermidine and spermine in the transgenic animals, the contents of the higher polyamines only transiently increased upon zinc administration and then returned to the basal level. These findings once again indicate that mammalian cells possess extremely powerful regulatory machinery to prevent an over-accumulation of spermidine and spermine in non-dividing cells, and that very high tissue putrescine concentrations can be tolerated, at least for periods of a few days, with seemingly no phenotypic changes.

scholarly journals Sex Differences in Postischemic Neuronal Necrosis in Gerbils

1991 ◽  
Vol 11 (2) ◽  
pp. 292-298 ◽  
Author(s):  
Edward D. Hall ◽  
Kay E. Pazara ◽  
Kelley L. Linseman
Keyword(s):  
Lipid Peroxidation ◽  
Cerebral Cortex ◽  
Vitamin E ◽  
Protective Efficacy ◽  
Neuronal Population ◽  
Mongolian Gerbils ◽  
Neuronal Necrosis ◽  
Male And Female ◽  
Endogenous Estrogen

Twenty-four hour postischemic neuronal necrosis was compared in male vs. female Mongolian gerbils subjected to a 3-h period of severe incomplete hemispheric ischemia produced by unilateral carotid occlusion. The incidence of stroke-prone males was 42.9% versus 26.7% for the females. Among the stroke-prone animals, the males displayed significantly greater neuronal necrosis at 24 h after ischemia compared to the females in the cerebral cortex and CA, region of the hippocampus. In the CA, region of the stroke-prone males, only 2.0% of the normal neuronal population remained by 24 h compared to 36.8% in the stroke-prone females (p < 0.02). In the cerebral cortex, the males had only 19.9% of normal versus 58.2% in the females (p < 0.05). In a second series of mechanistic experiments, no differences in cortical blood flow (CBF) were disclosed between preselected male and female stroke-prone animals before, during, or for 2 h after ischemia. As with the CBF, the extent of cortical extracellular hypocalcia during ischemia did not differ significantly. However, the degree of postischemic recovery of cortical extracellular calcium was significantly better in the females from 30 min to 2 h after reperfusion. In the same experiments, hemispheric vitamin E levels were measured at the 2 h time point as an index of postischemic brain lipid peroxidation. No difference in baseline vitamin E levels was observed between male and female sham-operated gerbils. In the males subjected to 3 h of ischemia plus 2 h of reperfusion, the hemispheric vitamin E decreased by 43.5% compared to the sham-operated males. In contrast, the females displayed only a 4.2% decline (p < 0.05 versus males). Previous studies showing the protective efficacy of antioxidants in this model have suggested an important role of oxygen radical-induced lipid peroxidation. Thus, it is proposed that the lesser ischemic vulnerability of females may be based upon an antioxidant effect of endogenous estrogen. Indeed, estrogen was found to be a more potent inhibitor of iron-catalyzed lipid peroxidation in brain tissue than vitamin E.

scholarly journals The effects of 24R,25-dihydroxycholecalciferol and of 1 α,25-dihydroxycholecalciferol on ornithine decarboxylase activity and on DNA synthesis in the epiphysis and diaphysis of rat bone and in the duodenum

1983 ◽  
Vol 214 (2) ◽  
pp. 293-298 ◽  
Author(s):  
D Sömjen ◽  
I Binderman ◽  
Y Weisman
Keyword(s):  
Vitamin D ◽  
Enzyme Activity ◽  
Ornithine Decarboxylase ◽  
Thymidine Incorporation ◽  
Single Injection ◽  
Fold Increase ◽  
Decarboxylase Activity ◽  
Long Bones ◽  
Vitamin D Metabolites ◽  
Ornithine Decarboxylase Activity

The effect of cholecalciferol metabolites on ornithine decarboxylase activity and on DNA synthesis in developing long bones was investigated in vitamin D-depleted rats. In the epiphysis there was a 6.4-fold increase in ornithine decarboxylase activity 5 h after a single injection of 24R,25-dihydroxycholecalciferol but not of 24S,25-dihydroxycholecalciferol or other vitamin D metabolites. In comparison, in the diaphysis and duodenum, 1 alpha,25-dihydroxycholecalciferol, but not other vitamin D metabolites, caused a 3-3.5-fold increase in the enzyme activity. The enzyme activity in the tissues examined attained a maximal value at 5 h after the injection of the metabolites. The activity of ornithine decarboxylase in the epiphysial region increased dose-dependently as the result of a single injection of 24R,25-dihydroxycholecalciferol and attained a maximal value at a dose between 30 and 3000 ng. In addition, administration of 24R,25-dihydroxycholecalciferol, but not 24S,25-dihydroxycholecalciferol or other metabolites, caused within 24 h a 1.7-2.0-fold increase in [3H]thymidine incorporation into DNA of the epiphyses of tibial bones. In comparison, 1 alpha,25-dihydroxycholecalciferol caused a 1.5-fold increase in [3H]thymidine incorporation into DNA of the diaphyses and of the duodenum. The present data indicate that 24R,25-dihydroxycholecalciferol is involved in the regulation of epiphyseal growth, whereas 1 alpha,25,dihydroxycholecalciferol stimulates the proliferation of cells in the diaphysis of long bones and in the intestinal mucosa.

Ornithine Decarboxylase Activity and Edema Formation in Cerebral Ischemia of Conscious Gerbils

2002 ◽  
Vol 65 (6) ◽  
pp. 2639-2643 ◽  
Author(s):  
A. Muralikrishna Rao ◽  
Mustafa K. Başkaya ◽  
Mary E. Maley ◽  
M. Renuka Prasad ◽  
Robert J. Dempsey
Keyword(s):  
Cerebral Ischemia ◽  
Ornithine Decarboxylase ◽  
Decarboxylase Activity ◽  
Edema Formation ◽  
Ornithine Decarboxylase Activity

scholarly journals Ornithine decarboxylase activity in insulin-deficient states

1980 ◽  
Vol 192 (2) ◽  
pp. 725-732 ◽  
Author(s):  
Cheryl A. Conover ◽  
S. Jaime Rozovski ◽  
Eva R. Belur ◽  
Thomas T. Aoki ◽  
Neil B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Ornithine Decarboxylase ◽  
Fold Increase ◽  
Diabetic Rats ◽  
Decarboxylase Activity ◽  
Promoting Effect ◽  
Comparable Group ◽  
Peripheral Tissues ◽  
Ornithine Decarboxylase Activity ◽  
Second Peak

The activity of ornithine decarboxylase, the rate-controlling enzyme in polyamine biosynthesis, was determined in tissues of normal control rats and rats made diabetic with streptozotocin. In untreated diabetic rats fed ad libitum, ornithine decarboxylase activity was markedly diminished in liver, skeletal muscle, heart and thymus. Ornithine decarboxylase was not diminished in a comparable group of diabetic rats maintained on insulin. Starvation for 48h decreased ornithine decarboxylase activity to very low values in tissues of both normal and diabetic rats. In the normal group, refeeding caused a biphasic increase in liver ornithine decarboxylase; there was a 20-fold increase in activity at 3h followed by a decrease in activity, and a second peak between 9 and 24h. Increases in ornithine decarboxylase in skeletal muscle, heart and thymus were not evident until after 24–48h of refeeding, and only a single increase occurred. The increase in liver ornithine decarboxylase in diabetic rats was greater than in normal rats after 3h of refeeding, but there was no second peak. In peripheral tissues, the increase in ornithine decarboxylase with refeeding was diminished. Skeletal-muscle ornithine decarboxylase is induced more rapidly when meal-fed rats are refed after a period without food. Refeeding these rats after a 48h period without food caused a 5-fold increase in ornithine decarboxylase in skeletal muscle at 3h in control rats but failed to increase activity in diabetic rats. When insulin was administered alone or together with food to the diabetic rats, muscle ornithine decarboxylase increased to activities even higher than in the refed controls. In conclusion, these findings indicate that the regulation of ornithine decarboxylase in many tissues is grossly impaired in diabetes and starvation. They also suggest that polyamine formation in vivo is an integral component of the growth-promoting effect of insulin or some factor dependent on insulin.

scholarly journals Temporary Focal Cerebral Ischemia Results in Swollen Astrocytic End-Feet That Compress Microvessels and Lead to Focal Cortical Infarction

2010 ◽  
Vol 31 (1) ◽  
pp. 328-338 ◽  
Author(s):  
Umeo Ito ◽  
Yoji Hakamata ◽  
Emiko Kawakami ◽  
Kiyomitsu Oyanagi
Keyword(s):  
Cerebral Cortex ◽  
Cerebral Ischemia ◽  
Microvascular Obstruction ◽  
Focal Cerebral Ischemia ◽  
Abrupt Onset ◽  
Stroke Index ◽  
Neuronal Necrosis ◽  
Temporary Ischemia ◽  
Electron Microscopical ◽  
Cut Surface

We examined the mechanisms underlying the abrupt onset of the focal infarction in disseminated selective neuronal necrosis (DSNN) after temporary ischemia. Stroke-positive animals were selected according to their stroke-index score during the first 10 minutes after left carotid occlusion performed twice at a 5-hour interval. The animals were euthanized at various times after the second ischemia. Light- and electron-microscopical studies were performed chronologically on the coronal-cut surface of the cerebral cortex at the chiasmatic level, where focal infarction evolved in the maturing DSNN. We counted the number of neurons, astrocytes, and astrocytic processes (APs); measured the areas of end-feet and astrocytes; and counted the numbers of obstructed microvessels and carbon-black-suspension-perfused microvessels (CBSPm). Between 0.5 and 5 hours after ischemia, DSNN matured, with the numbers of degenerated and dead neurons increasing, and those of APs cut-ends decreasing; whereas the area of the end-feet and the numbers of obstructed microvessels increased and those of CBSPm decreased. At 12 and 24 hours after ischemia, the infarction evolved, with the area of end-feet and astrocytic number decreased; whereas the numbers of obstructed microvessels decreased and the CBSPm number increased. The focal infarction evolved by temporary microvascular obstruction because of compression by swollen end-feet.

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