scholarly journals Mechanisms of Melatonin-Induced Protection in the Brain of Late Gestation Fetal Sheep in Response to Hypoxia

2012 ◽  
Vol 34 (6) ◽  
pp. 543-551 ◽  
Author(s):  
Tamara Yawno ◽  
Margie Castillo-Melendez ◽  
Graham Jenkin ◽  
Euan M. Wallace ◽  
David W. Walker ◽  
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1995 ◽  
Vol 675 (1-2) ◽  
pp. 303-315 ◽  
Author(s):  
T.J. McDonald ◽  
C. Li ◽  
R.H. Wasserman

2015 ◽  
Vol 308 (3) ◽  
pp. R151-R162 ◽  
Author(s):  
Rajan Poudel ◽  
I. Caroline McMillen ◽  
Stacey L. Dunn ◽  
Song Zhang ◽  
Janna L. Morrison

In the fetus, there is a redistribution of cardiac output in response to acute hypoxemia, to maintain perfusion of key organs, including the brain, heart, and adrenal glands. There may be a similar redistribution of cardiac output in the chronically hypoxemic, intrauterine growth-restricted fetus. Surgical removal of uterine caruncles in nonpregnant ewe results in the restriction of placental growth (PR) and intrauterine growth. Vascular catheters were implanted in seven control and six PR fetal sheep, and blood flow to organs was determined using microspheres. Placental and fetal weight was significantly reduced in the PR group. Despite an increase in the relative brain weight in the PR group, there was no difference in blood flow to the brain between the groups, although PR fetuses had higher blood flow to the temporal lobe. Adrenal blood flow was significantly higher in PR fetuses, and there was a direct relationship between mean gestational PaO2 and blood flow to the adrenal gland. There was no change in blood flow, but a decrease in oxygen and glucose delivery to the heart in the PR fetuses. In another group, there was a decrease in femoral artery blood flow in the PR compared with the Control group, and this may support blood flow changes to the adrenal and temporal lobe. In contrast to the response to acute hypoxemia, these data show that there is a redistribution of blood flow to the adrenals and temporal lobe, but not the heart or whole brain, in chronically hypoxemic PR fetuses in late gestation.


1995 ◽  
Vol 7 (3) ◽  
pp. 377 ◽  
Author(s):  
EK Kim ◽  
CE Wood ◽  
M Keller-Wood

11 Beta-hydroxysteroid dehydrogenase (11 beta-HSD) converts 11-hydroxycorticosteroids to 11-oxocorticosteroids, thereby influencing the availability of bioactive cortisol or corticosterone in target tissues. The activity of this enzyme was investigated in sheep by: (1) measuring relative 11 beta-HSD activities in kidney, liver and placenta, and in various areas of the brain (hypothalamus, hippocampus, and brainstem); (2) characterizing the optimum pH of activities in the tested tissues; (3) investigating the possible effect of gonadal steroids on 11 beta-HSD activity in adult hypothalamus and kidney; and (4) investigating possible developmental changes in activities in the tested tissues. The optimum pH in liver and placenta was pH 9-10, whereas the optimum pH in kidney was pH 7-8. In tissues from adult ewes, 11 beta-HSD activity was highest in liver (84.6 +/- 3.8%) and kidney (49.8 +/- 11.6%), lower but measurable in pituitary (38.8 +/- 3.7%), and near the limit of detection in hypothalamus and hippocampus (2.7 +/- 0.9% and 3.2 +/- 0.8% respectively). Liver, kidney and pituitary from late-gestation fetal sheep contained activities which were similar to those in the adult (76.9 +/- 4.5%, 66.0 +/- 6.7% and 26.3 +/- 3.0% respectively). Activity in the pituitary was not related to fetal gestational age. Placenta also contained measureable 11 beta-HSD activity (21.4 +/- 4.7%). However, no activity was detected in hypothalamus (-1.7 +/- 0.2%), hippocampus (-0.2 +/- 0.6%) or brainstem (-1.0 +/- 0.6%) in late-gestation fetal or neonatal sheep. Enzyme activities in kidney and hypothalamus did not change significantly when the circulating concentrations of ovarian steroids were altered over a 1-3-week period. It is concluded that the ovine kidney, liver and placenta, but not hypothalamus or cerebral cortex, contain 11 beta-HSD activity. In addition, there is no change in 11 beta-HSD activity between late-gestation fetal life and adult life, and the relative activities are not altered by the ovarian steroid milieu.


2000 ◽  
Vol 88 (1) ◽  
pp. 82-90 ◽  
Author(s):  
J. P. Newman ◽  
D. M. Peebles ◽  
S. R. G. Harding ◽  
R. Springett ◽  
M. A. Hanson

The purpose of this study was to investigate metabolic and hemodynamic responses in two fetal tissues, hindlimb muscle and brain, to an episode of acute moderate asphyxia. Near-infrared spectroscopy was used to measure changes in total hemoglobin concentration ([tHb]) and the redox state of cytochrome oxidase (COX) simultaneously in the brain and hindlimb of near-term unanesthetized fetal sheep in utero. Oxygen delivery (Do 2) to, and consumption (V˙o 2) by, each tissue was derived from the arteriovenous difference in oxygen content and blood flow, measured by implanted flow probes. One hour of moderate asphyxia ( n = 11), caused by occlusion of the maternal common internal iliac artery, led to a significant fall in Do 2to both tissues and to a significant drop inV˙o 2 by the head. This was associated with an initial fall in redox state COX in the leg but an increase in the brain. [tHb], and therefore blood volume, fell in the leg and increased in the brain. These data suggest the presence of a fetal metabolic response to hypoxia, which, in the brain, occurs rapidly and could be neuroprotective.


1997 ◽  
Vol 272 (4) ◽  
pp. R1235-R1244 ◽  
Author(s):  
R. M. Abrams ◽  
D. J. Burchfield ◽  
Y. Sun ◽  
C. B. Smith

During gestation there is likely to be a constantly changing rate of protein synthesis in the brain that may exhibit regional specificity. With the use of the quantitative autoradiographic L-[1-(14)C]leucine method for the determination of local rates of leucine incorporation into cerebral protein (lCPS(Leu)), we have sought to characterize this important process. lCPS(Leu) was measured in nine fetal sheep (118-139 days gestational age) and five newborn lambs (1-5 days of age). In other experiments, the fraction of leucine in the precursor pool for protein synthesis in the brain derived from the arterial plasma was determined to be 0.57 +/- 0.04 (mean +/- SE) in one fetus and two lambs. This value was used in the calculation of lCPS(Leu) in 35 regions of the central nervous system, pineal body, and whole brain. Regardless of age, lCPS(Leu) was highest in the pineal body, brain stem, and hypothalamic nuclei and lowest in white matter. In sensorimotor cortex, corona radiata, pyramidal tracts, and whole brain, lCPS(Leu) was positively correlated with prenatal age (P < or = 0.05). These increases in lCPS(Leu) probably reflect myelination in the cerebrum, which is known to occur in late gestation.


1985 ◽  
Vol 249 (1) ◽  
pp. E115-E120
Author(s):  
F. H. Morriss ◽  
R. N. Marshall ◽  
S. S. Crandell ◽  
B. J. Fitzgerald ◽  
L. Riddle

In vitro assays for [35S]sulfate uptake by ovine fetal costal cartilage were used to assess gestational changes in cartilage metabolism. Addition of 20% normal human serum to the incubation medium increased fetal cartilage [35S]sulfate incorporation into glycosaminoglycans. Both basal and human serum-stimulated uptakes of [35S]sulfate by fetal sheep cartilage decreased from midgestation to full term. The incremental response in [35S]sulfate uptake that was stimulated by human serum decreased as gestation proceeded to full-term. Fetal serum sulfate concentration decreased logarithmically during gestation, raising the possibility that cartilage sulfate uptake might become substrate limited as full term is approached. Perfusion of seven late gestation sheep fetuses for 7 days with Na2SO4 to achieve serum sulfate concentrations similar to those observed earlier in gestation resulted in a 33% increase in mean cartilage [35S]sulfate uptake compared with that of control twin fetuses, but uptake was not increased to values that occurred spontaneously earlier in gestation. These results suggest that the decreasing rate of [35S]sulfate uptake by fetal cartilage during the last half of gestation is associated only minimally with decreasing serum sulfate levels and is most consistent with intrinsic change in resting chondrocyte metabolism during gestation.


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