scholarly journals Intra-Amniotic LPS Induced Region-Specific Changes in Presynaptic Bouton Densities in the Ovine Fetal Brain

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Eveline Strackx ◽  
Reint K. Jellema ◽  
Rebecca Rieke ◽  
Ruth Gussenhoven ◽  
Johan S. H. Vles ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Dentate Gyrus ◽  
Somatosensory Cortex ◽  
Fetal Brain ◽  
Control Group ◽  
Fetal Sheep ◽  
Increased Risk ◽  
Sheep Brain ◽  
Presynaptic Density ◽  
Ovine Fetal

Rationale. Chorioamnionitis has been associated with increased risk for fetal brain damage. Although, it is now accepted that synaptic dysfunction might be responsible for functional deficits, synaptic densities/numbers after a fetal inflammatory challenge have not been studied in different regions yet. Therefore, we tested in this study the hypothesis that LPS-induced chorioamnionitis caused profound changes in synaptic densities in different regions of the fetal sheep brain.Material and Methods. Chorioamnionitis was induced by a 10 mg intra-amniotic LPS injection at two different exposure intervals. The fetal brain was studied at 125 days of gestation (term = 150 days) either 2 (LPS2D group) or 14 days (LPS14D group) after LPS or saline injection (control group). Synaptophysin immunohistochemistry was used to quantify the presynaptic density in layers 2-3 and 5-6 of the motor cortex, somatosensory cortex, entorhinal cortex, and piriforme cortex, in the nucleus caudatus and putamen and in CA1/2, CA3, and dentate gyrus of the hippocampus.Results. There was a significant reduction in presynaptic bouton densities in layers 2-3 and 5-6 of the motor cortex and in layers 2-3 of the entorhinal and the somatosensory cortex, in the nucleus caudate and putamen and the CA1/2 and CA3 of the hippocampus in the LPS2D compared to control animals. Only in the motor cortex and putamen, the presynaptic density was significantly decreased in the LPS14 D compared to the control group. No changes were found in the dentate gyrus of the hippocampus and the piriforme cortex.Conclusion. We demonstrated that LPS-induced chorioamnionitis caused a decreased density in presynaptic boutons in different areas in the fetal brain. These synaptic changes seemed to be region-specific, with some regions being more affected than others, and seemed to be transient in some regions.

Heat production of fetal sheep brain in utero

1977 ◽  
Vol 43 (4) ◽  
pp. 747-749 ◽  
Author(s):  
R. M. Abrams ◽  
J. F. Clapp ◽  
M. Notelovitz ◽  
T. Tyler ◽  
S. Cassin
Keyword(s):  
Specific Heat ◽  
Heat Production ◽  
Brain Temperature ◽  
Main Pulmonary Artery ◽  
Fetal Brain ◽  
In Utero ◽  
Total Occlusion ◽  
Fetal Sheep ◽  
Sheep Brain ◽  
Near Term

Thermojunctions were implanted in the brains of 10 near term fetal sheep in utero under halothane anesthesia. Brief total occlusion of fetal brachiocephalic artery was followed immediately by an increase in brain temperature (mean +/- SE) of 0.130 +/- 0.014 degrees C-min-1. Occlusion of main pulmonary artery and ascending aorta, simultaneously, led to a brain temperature increase of 0.144 +/- 0.018 degrees C-min-1. Specific heat of three fetal brains was determined to be 0.898 +/- 0.014 cal-g-1. degrees C-1 or 3.76 +/- 0.059 J-g-1. Rate of fetal brain heat production, computed as the product of the higher rate of temperature change and brain specific heat, was 0.129 +/- 0.014 cal-g-1-min-1 or 9.00 +/- 0.98 mW-g-1.

Effect of intermittent umbilical cord occlusion on fetal respiratory activity and brain adenosine in late-gestation sheep

2002 ◽  
Vol 14 (1) ◽  
pp. 35 ◽  
Author(s):  
Carole S. Watson ◽  
Rachel Schaefer ◽  
Susan E. White ◽  
Jacobus H. Homan ◽  
Laurence Fraher ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Fetal Brain ◽  
Extracellular Fluid ◽  
Inhibitory Effect ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Arterial Ph ◽  
Tracheal Pressure ◽  
Ovine Fetal ◽  
Arterial Po2

It was hypothesized that intermittent umbilical cord occlusion (UCO) would inhibit ovine fetal breathing movements (FBM) in association with increased cerebral adenosine levels. To test this hypothesis, on two successive days during late gestation (133–134 days; term = 146 days), microdialysis samples were collected from the brains of 10 chronically instrumented fetal sheep during 2-h periods of complete UCO induced every 30 min (Day 1: 2-min UCOs; Day 2: 4-min UCOs). Control fetuses (n = 10) underwent no UCO. Tracheal pressure was measured throughout. This regimen resulted in a decrease in fetal arterial PO2 (PaO2) during each UCO to 7.3 0.8 mmHg (P<0.01; Day 1) and 8.4 1.1 mmHg (P<0.01; Day 2). Throughout each UCO period, fetal arterial pH (pHa) decreased to 7.28 0.02 (P<0.01; Day 1) and 7.11 0.07 (P<0.01; Day 2). The hourly incidence of FBM decreased significantly only on Day 2, from 38.6 4.1% to 4.1 1.6% (P<0.01). The frequency of deep isolated inspiratory efforts increased from 4.7 2.0 h–1 to 17.6 6.1 h–1 (P<0.05; Day 1) and from 2.2 0.9 h–1 to 33.6 4 h–1 (P<0.01; Day 2). The amplitude of both FBM and deep isolated inspiratory efforts increased during the UCO periods on both days. The concentration of cerebral extracellular fluid (ECF) adenosine during UCO increased by 219 215% (P<0.05; Day 1) and 172 107% (P<0.05; Day 2) over the baseline periods. In conclusion, the severity of the inhibitory effect of repeated UCO on FBM depends, in part, on the length of the occlusions. The inhibition of FBM during intermittent UCO may be mediated by the increase in ECF adenosine in the fetal brain. Furthermore, FBM and deep isolated inspiratory efforts appear to be regulated by different mechanisms.

scholarly journals Genomics of estradiol-3-sulfate action in the ovine fetal hypothalamus

2012 ◽  
Vol 44 (13) ◽  
pp. 669-677 ◽  
Author(s):  
Maria Belen Rabaglino ◽  
Elaine Richards ◽  
Nancy Denslow ◽  
Maureen Keller-Wood ◽  
Charles E. Wood
Keyword(s):  
Feeding Behavior ◽  
Transforming Growth Factor ◽  
Fetal Brain ◽  
Ovis Aries ◽  
Late Gestation ◽  
Postnatal Life ◽  
Growth Factor Signaling ◽  
Fetal Sheep ◽  
Ovine Fetal ◽  
Agouti Related Protein

In fetal sheep during late gestation sulfoconjugated estrogens in plasma reach a concentration 40–100 times greater than unconjugated estrogens. The objective of the present study was to determine the genomics of estradiol-3-sulfate (E2S) action in the ovine fetal brain. The hypothesis was that E2S stimulates genes involved in the neuroendocrine pathways that direct or facilitate fetal development at the end of gestation. Four sets of chronically catheterized ovine twin fetuses were studied (gestational age: 120–127 days gestation) with one infused with E2S intracerebroventricularly (1 mg/day) and the other remaining untreated (control). After euthanasia, mRNA samples were extracted from fetal brains. Only hypothalamic samples were employed for this study given the important function of this brain region in the control of the hypothalamus-pituitary-adrenal axis. Microarray analysis was performed following the Agilent protocol for one-color 8 × 15 microarrays, designed for Ovis aries. A total of 363 known genes were significantly upregulated by the E2S treatment ( P < 0.05). Network and enrichment analyses were performed using the Cytoscape/Bingo software, and the results validated by quantitative real-time PCR. The main overrepresented biological processes resulting from this analysis were feeding behavior, hypoxia response, and transforming growth factor signaling. Notably, the genes involved in the feeding behavior (neuropeptide Y and agouti-related protein) were the most strongly induced by the E2S treatment. In conclusion, E2S may be an important component of the mechanism for activating orexigenic, hypoxia responsiveness and neuroprotective pathways in the lamb as it approaches postnatal life.

Glutamate Release from the Ovine Fetal Brain during Maternal Hemorrhage 

1995 ◽  
Vol 82 (2) ◽  
pp. 521-530 ◽  
Author(s):  
Donald H. Penning ◽  
David H. Chestnut ◽  
Franklin Dexter ◽  
James Hrdy ◽  
Dan Poduska ◽  
...  
Keyword(s):  
Parietal Cortex ◽  
Glutamate Release ◽  
Recovery Period ◽  
Fetal Brain ◽  
In Utero ◽  
Extracellular Glutamate ◽  
Microdialysis Probe ◽  
Fetal Sheep ◽  
Near Term ◽  
Ovine Fetal

Background Glutamate has been implicated in the pathophysiology of neuronal injury associated with cerebral hypoxia-ischemia. A model using chronic in utero microdialysis was developed to sample the extracellular space of the fetal brain. Using this model, we tested the hypothesis that glutamate efflux from the parasagittal parietal cortex of near-term fetuses would increase during maternal hemorrhage. Methods Twelve near-term fetal sheep were instrumented with vascular catheters, and a microdialysis probe(s) was implanted into the parasagittal parietal cortex. After a 3-day recovery period, the animals were subjected to maternal hemorrhage until either the fetal pH was &lt; 7.00 or the fetus died. The extracellular glutamate concentration in the collected dialysate was determined by high pressure liquid chromatography (HPLC). Results Maternal hemorrhage resulted in an 80-90% decrease in uterine blood flow, a decrease fetal po2, and a mixed metabolic and respiratory fetal acidosis. There were two groups of fetuses, survivors (n = 5) and nonsurvivors (n = 7). The nonsurvivor group showed a large increase (10-30-fold) in peak glutamate release (P = 0.0015). Survivors demonstrated a small (threefold) increase that was not statistically significant (P = 0.065), unless one animal with very low probe recovery was excluded (P = 0.0048). Conclusions Extracellular glutamate release from the fetal brain can occur during maternal hemorrhage with fetal acidemia. The pathophysiologic role (if any) of glutamate release in the survivors remains to be elucidated. Our results are consistent with the hypothesis that in utero release of glutamate occurs during periods of fetal asphyxia. This experimental preparation of chronic fetal brain microdialysis can be used to monitor the brain extracellular concentration of any dialyzable substance in response to stress, including maternal hemorrhage.

Novel method for in vivo hydroxyl radical measurement by microdialysis in fetal sheep brain in utero

2005 ◽  
Vol 98 (6) ◽  
pp. 2304-2310 ◽  
Author(s):  
Edwin B. Yan ◽  
Jessica K. Unthank ◽  
Margie Castillo-Melendez ◽  
Suzanne L. Miller ◽  
Steven J. Langford ◽  
...  
Keyword(s):  
Hydroxyl Radical ◽  
High Performance ◽  
Fetal Brain ◽  
In Utero ◽  
In Vivo Studies ◽  
Fetal Sheep ◽  
Low Concentrations ◽  
Sheep Brain

Hydroxyl radical (·OH) is a reactive oxygen species produced during severe hypoxia, asphyxia, or ischemia that can cause cell death resulting in brain damage. Generation of ·OH may occur in the fetal brain during asphyxia in utero. The very short half-life of ·OH requires use of trapping agents such as salicylic acid or phenylalanine for detection, but their hydroxylated derivatives are either unstable, produced endogenously, or difficult to measure in the small volume of microdialysis samples. In the present study, we used terephthalic acid (TA), hydroxylation of which yields a stable and highly fluorometric isomer (excitation, 326 nm; emission, 432 nm). In vitro studies using ·OH generated by the Fenton reaction showed that hydroxylated TA formed quickly (<10 s), was resistant to bleaching (<5% change in fluorescence), and permitted detection of <0.5 pmol ·OH. In vivo studies were performed in fetal sheep using microdialysis probes implanted into the parasagittal cortex. The probe was perfused at 2 μl/min with artificial cerebrospinal fluid containing 5 mM TA, and samples were collected every 30 min. Fluorescence measured in 10 μl of dialysate was significantly greater than in the efflux from probes perfused without TA. High-performance liquid chromotography analysis showed that the fluorescence in dialysis samples was entirely due to hydroxylation of TA. Thus this study shows that it is possible to use TA as a trapping agent for detecting low concentrations of ·OH both in vitro and in vivo and that low concentrations of ·OH are present in fetal brain tissue and fluctuate with time.

scholarly journals Fetal Hypothalamus-Pituitary-Adrenal Responses to Estradiol Sulfate

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4966-4973 ◽  
Author(s):  
Charles E. Wood
Keyword(s):  
Fetal Brain ◽  
Control Group ◽  
Cortisol Secretion ◽  
Acth Secretion ◽  
Fetal Sheep ◽  
Adrenal Axis ◽  
Arterial Blood ◽  
Hypothalamus Pituitary Adrenal Axis ◽  
Near Term ◽  
Pituitary Adrenal Axis

Estradiol (E2) is an important modifier of the activity of the fetal hypothalamus-pituitary-adrenal axis. We have reported that estradiol-3-sulfate (E2SO4) circulates in fetal blood in far higher concentrations than E2 and that the fetal brain expresses steroid sulfatase, required for local deconjugation of E2SO4. We performed the present study to test the hypothesis that chronic infusion of E2SO4 chronically increases ACTH and cortisol secretion and that it shortens gestation. Chronically catheterized fetal sheep were treated with E2SO4 intracerebroventricular (n = 5), E2SO4 iv (n = 4), or no steroid infusion (control group, n = 5). Fetuses were subjected to arterial blood sampling every other day until spontaneous birth for plasma hormone analysis. Treatment with E2SO4 attenuated preparturient increases in ACTH secretion near term without affecting the ontogenetic rise in plasma cortisol. Infusion of E2SO4 intracerebroventricularly significantly increased plasma E2, plasma E2SO4, and plasma progesterone and shortened gestation compared with all other groups. These results are consistent with the conclusion that E2SO4: 1) interacts with the hypothalamus-pituitary-adrenal axis primarily by stimulating cortisol secretion and inhibiting ACTH and pro-ACTH secretion by negative feedback; and 2) stimulates the secretion of E2 and E2SO4. We conclude that the endocrine response to E2SO4 in the fetus is not identical with the response to E2.

Lipopolysaccharide-Induced Preconditioning Attenuates Apoptosis and Differentially Regulates TLR4 and TLR7 Gene Expression after Ischemia in the Preterm Ovine Fetal Brain

2015 ◽  
Vol 37 (6) ◽  
pp. 497-514 ◽  
Author(s):  
Simerdeep K. Dhillon ◽  
Alistair J. Gunn ◽  
Yewon Jung ◽  
Sam Mathai ◽  
Laura Bennet ◽  
...  
Keyword(s):  
Microglial Activation ◽  
Low Dose ◽  
Fetal Brain ◽  
Acute Ischemia ◽  
Dependent Manner ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Important Mediator ◽  
Cellular Apoptosis ◽  
Ovine Fetal

Acute exposure to subclinical infection modulates subsequent hypoxia-ischemia (HI) injury in a time-dependent manner, likely by cross-talk through Toll-like receptors (TLRs), but the specific pathways are unclear in the preterm-equivalent brain. In the present study, we tested the hypothesis that repeated low-dose exposure to lipopolysaccharide (LPS) before acute ischemia would be associated with induction of specific TLRs that are potentially neuroprotective. Fetal sheep at 0.65 gestation (term is ∼145 days) received intravenous boluses of low-dose LPS for 5 days (day 1, 50 ng/kg; days 2-5, 100 ng/kg) or the same volume of saline. Either 4 or 24 h after the last bolus of LPS, complete carotid occlusion was induced for 22 min. Five days after LPS, brains were collected. Pretreatment with LPS for 5 days decreased cellular apoptosis, microglial activation and reactive astrogliosis in response to HI injury induced 24 but not 4 h after the last dose of LPS. This was associated with upregulation of TLR4, TLR7 and IFN-β mRNA, and increased fetal plasma IFN-β concentrations. The association of reduced white matter apoptosis and astrogliosis after repeated low-dose LPS finishing 24 h but not 4 h before cerebral ischemia, with central and peripheral induction of IFN-β, suggests the possibility that IFN-β may be an important mediator of endogenous neuroprotection in the developing brain.

Adaptation of laser-Doppler flowmetry to measure cerebral blood flow in the fetal sheep

2000 ◽  
Vol 89 (3) ◽  
pp. 1065-1071 ◽  
Author(s):  
Jiang Lan ◽  
Christian J. Hunter ◽  
Tomoaki Murata ◽  
Gordon G. Power
Keyword(s):  
Laser Doppler Flowmetry ◽  
Cerebral Perfusion ◽  
Recovery Period ◽  
Fetal Brain ◽  
Laser Doppler ◽  
Fetal Sheep ◽  
Doppler Flowmetry ◽  
Movement Artifact ◽  
Movement Artifacts ◽  
Ovine Fetal

The purpose of this study was to devise a means to use laser-Doppler flowmetry to measure cerebral perfusion before birth. The method has not been used previously, largely because of intrauterine movement artifacts. To minimize movement artifacts, a probe holder was molded from epoxy putty to the contour of the fetal skull. A curved 18-gauge needle was embedded in the holder. At surgery, the holder, probe, and skull were fixed together with tissue glue. Residual signals were recorded after fetal death and after maternal death 1 h later. These averaged <5% of baseline flow signals, indicating minimal movement artifact. To test the usefulness of the method, cerebral flow responses were measured during moderate fetal hypoxia induced by giving the ewes ∼10% oxygen in nitrogen to breathe. As fetal arterial Po 2 decreased from 21.1 ± 0.5 to 10.7 ± 0.4 Torr during a 30-min period, cerebral perfusion increased progressively to 56 ± 8% above baseline. Perfusion then returned to baseline levels during a 30-min recovery period. These responses are quantitatively similar to those spot observations that have been recorded earlier using labeled microspheres. We conclude that cerebral perfusion can be successfully measured by using laser-Doppler flowmetry with the unanesthetized, chronically prepared fetal sheep as an experimental model. With this method, relative changes of perfusion from a small volume of the ovine fetal brain can be measured on a continuous basis, and movement artifacts can be reduced to 5% of measured flow values.

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

2018 ◽  
Vol 27 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Gintare Dargiene ◽  
Greta Streleckiene ◽  
Jurgita Skieceviciene ◽  
Marcis Leja ◽  
Alexander Link ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Genetic Polymorphisms ◽  
Association Studies ◽  
Control Group ◽  
Similar Distribution ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Infection Susceptibility ◽  
H Pylori

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum.Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed.Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG.

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