scholarly journals In utero hypoxia altered Ang II-induced contraction via PKCβ in fetal cerebral arteries

2020 ◽  
Vol 244 (1) ◽  
pp. 213-222
Author(s):  
Hongyu Su ◽  
Xueyi Chen ◽  
Yueming Zhang ◽  
Linglu Qi ◽  
Yun He ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cerebral Circulation ◽  
Cerebral Arteries ◽  
Fetal Brain ◽  
Calcium Transient ◽  
In Utero ◽  
Protective Effects ◽  
Ang Ii ◽  
Voltage Dependent ◽  
Near Term

Cerebral circulation is important in fetal brain development, and angiotensin II (Ang II) plays vital roles in regulation of adult cerebral circulation. However, functions of Ang II in fetal cerebral vasculature and influences of in utero hypoxia on Ang II-mediated fetal cerebral vascular responses are largely unknown. This study investigated the effects and mechanisms of in utero hypoxia on fetal middle cerebral arteries (MCA) via Ang II. Near-term ovine fetuses were exposed to in utero hypoxia, and fetal MCA responses to Ang II were tested for vascular tension, calcium transient, and molecular analysis. Ang II caused significant dose-dependent contraction in control fetal MCA. Ang II-induced MCA constriction was decreased significantly in hypoxic fetuses. Neither losartan (AT1R antagonist, 10−5 mol/L) nor PD123,319 (AT2R antagonist, 10−5 mol/L) altered Ang II-mediated contraction in fetal MCA. Phenylephrine-mediated constriction was also significantly weaker in hypoxic fetuses. Bay K8644 caused similar contractions between the two groups. Protein expression of L-type voltage-dependent calcium channels was unchanged. There were no differences in caffeine-mediated vascular tension or calcium transients. Contraction induced by PDBu (PKC agonist) was obviously weaker in hypoxic MCA. Protein expression of PKCβ was reduced in the hypoxic compared with the control, along with no differences in phosphorylation levels. The results showed that fetal MCA was functionally responsive to Ang II near term. Intrauterine hypoxia reduced the vascular agonist-mediated contraction in fetal MCA, probably via decreasing PKCβ and its phosphorylation, which might play protective effects on fetal cerebral circulation against transient hypoxia.

Central angiotensin induction of fetal brain c-fos expression and swallowing activity

2001 ◽  
Vol 280 (6) ◽  
pp. R1837-R1843 ◽  
Author(s):  
Zhice Xu ◽  
Calvario Glenda ◽  
Linda Day ◽  
Jiaming Yao ◽  
Michael G. Ross
Keyword(s):  
Body Fluid ◽  
Drinking Behavior ◽  
Fetal Brain ◽  
Cellular Responses ◽  
Ang Ii ◽  
Preoptic Nucleus ◽  
Median Preoptic Nucleus ◽  
Fluid Regulation ◽  
Fos Expression ◽  
Near Term

The present study examined physiological and cellular responses to central application of ANG II in ovine fetuses and determined the fetal central ANG-mediated dipsogenic sites in utero. Chronically prepared near-term ovine fetuses (130 ± 2 days) received injection of ANG II (1.5 μg/kg icv). Fetuses were monitored for 3.5 h for swallowing activity, after which animals were killed and fetal brains were perfused for subsequent Fos staining. Intracerebroventricular ANG II significantly increased fetal swallowing in near-term ovine fetuses (1.1 ± 0.2 to 4.5 ± 1.0 swallows/min). The initiation of stimulated fetal swallowing activity was similar to the latency of thirst responses (drinking behavior) elicited by central ANG II in adult animals. ANG II evoked increased Fos staining in putative dipsogenic centers, including the subfornical organ, organum vasculosum of the lamina terminalis, and median preoptic nucleus. Intracerebroventricular injection of ANG II also caused c- fos expression in the fetal hindbrain. These results indicate that an ANG II-mediated central dipsogenic mechanism is intact before birth, acting at sites consistent with the dipsogenic neural network. Central ANG II mechanisms likely contribute to fetal body fluid and amniotic fluid regulation.

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.

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 < 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.

Neurologic Manifestations of In Utero Cocaine Exposure in Near-Term and Term Infants

PEDIATRICS ◽  
1995 ◽  
Vol 96 (2) ◽  
pp. 259-264
Author(s):  
Terri A. King ◽  
Jeffrey M. Perlman ◽  
Abbot R. Laptook ◽  
Nancy Rollins ◽  
Gregory Jackson ◽  
...  
Keyword(s):  
Flow Velocity ◽  
Intraventricular Hemorrhage ◽  
Anterior Cerebral Artery ◽  
Drug Withdrawal ◽  
Cerebral Arteries ◽  
In Utero ◽  
Neurologic Examination ◽  
Term Infants ◽  
Middle Cerebral Arteries ◽  
Near Term

Objective. To determine whether the incidence of neurosonographic and neurologic abnormalities is higher in cocaine-exposed infants at birth. Methods. In utero exposure to cocaine was investigated in 39 term and near-term infants with positive urine screens for cocaine only and 39 matched control infants without drug exposure admitted to the regular term newborn nursery. Serial evaluations were performed on each infant on postnatal days 1 and 2 and included a cranial sonogram, a neurologic and behavioral assessment for drug withdrawal, and Doppler interrogation of the anterior and middle cerebral arteries. Results. There were no differences between groups in neurosonographic abnormalities. Grade I or II intraventricular hemorrhage occurred in 11% of cocaine-exposed and 11% of control infants. There were no cases of grade III intraventricular hemorrhage, cystic periventricular leukomalacia, or neonatal stroke. Head size was smaller in cocaine-exposed infants, ie, 32.7 ± 0.1 cm versus 33.8 ± 0.1 cm. The neurologic examination was similar between groups with regard to tone, reflexes, and cranial nerves. Behavioral scores were higher on both days, in cocaine-exposed versus control infants, ie, 4.4 ± 0.5 versus 2.7 ± 0.3 on day 1 and 5.0 ± 0.5 versus 1.71 ± 0.31 on day 2. Cerebral blood flow velocity measurements in the anterior cerebral artery were similar between groups on both days of examination. However, cocaine-exposed infants demonstrated a significant increase in flow velocity from day 1 to day 2, ie, 0.48 ± 0.03 to 0.57 ± 0.04. There was a concomitant decrease in the pulsatility index from day 1 to day 2 in the cocaine-exposed, ie, 0.74 ± 0.02 to 0.69 ± 0.02, but not in the control infants. No differences were noted in the flow velocities in the middle cerebral arteries between groups. Conclusions. Term and near-term infants admitted to a regular nursery who are exposed to cocaine in utero: (1) do not exhibit an increased incidence of neurosonographic abnormalities; (2) do exhibit altered behavior consistent with drug withdrawal; and (3) do demonstrate changes in flow velocity in the anterior cerebral artery consistent with the vasoconstrictive effects of the drug. However, these changes were not accompanied by changes in the neurologic examination or altered care. The long-term neurodevelopmental implications of these subtle abnormalities in the neonatal period remain to be determined.

Osmotic threshold and sensitivity for vasopressin release and Fos expression by hypertonic NaCl in ovine fetus

2000 ◽  
Vol 279 (6) ◽  
pp. E1207-E1215 ◽  
Author(s):  
Zhice Xu ◽  
Calvario Glenda ◽  
Linda Day ◽  
Jiaming Yao ◽  
Michael G. Ross
Keyword(s):  
Fetal Brain ◽  
Plasma Osmolality ◽  
Ang Ii ◽  
Double Labeling ◽  
Fetal Sheep ◽  
Vasopressin Release ◽  
Fetal Plasma ◽  
Ovine Fetus ◽  
Near Term ◽  
Stimulation Of

In adults, hyperosmolality stimulates central osmoreceptors, resulting in arginine vasopressin (AVP) secretion. Near-term fetal sheep have also developed mechanisms to respond to intravascular hypertonicity with stimulation of in utero AVP release. However, prior studies demonstrating fetal AVP secretion have utilized plasma tonicity changes greater than those required for adult osmotically induced AVP stimulation. We sought to examine near-term fetal plasma osmolality threshold and sensitivity for stimulation of AVP secretion and to correlate plasma hormone levels with central neuronal responsiveness. Chronically instrumented ovine fetuses (130 ± 2 days) and maternal ewes simultaneously received either isotonic or hypertonic intravascular NaCl infusions. Maternal and fetal plasma AVP and angiotensin II (ANG II) levels were examined at progressively increasing levels of plasma hypertonicity. Intravenous hypertonic NaCl gradually elevated plasma osmolality and sodium levels. Both maternal and fetal plasma AVP increased during hypertonicity, whereas ANG II levels were not changed. Maternal AVP levels significantly increased with a 3% increase in plasma osmolality, whereas fetal plasma AVP significantly increased only at higher plasma osmolality levels (over 6%). Thus the slope of the regression of AVP vs. osmolality was greater for ewes than for fetuses (0.232 vs. 0.064), despite similar maternal and fetal plasma osmolality thresholds for AVP secretion (302 vs. 304 mosmol/kg). Hyperosmolality induced Fos immunoreactivity (FOS-ir) in the circumventricular organs of the fetal brain. FOS-ir was also demonstrated in the fetal supraoptic and paraventricular nuclei (SON and PVN), and double labeling demonstrated that AVP-containing neurons in the SON and PVN expressed Fos in response to intravenous NaCl. These results demonstrate that, in the ovine fetus at 130 days of gestation, neuroendocrine responses to cellular dehydration are functional, although they evidence a relatively reduced sensitivity for AVP secretion compared with the adult.

Neuropathology of the near-term and midgestation ovine fetal brain after sustained in utero hypoxemia

1994 ◽  
Vol 170 (5) ◽  
pp. 1425-1432 ◽  
Author(s):  
Donald H. Penning ◽  
Marjorie R. Grafe ◽  
Robert Hammond ◽  
Yoshio Matsuda ◽  
John Patrick ◽  
...  
Keyword(s):  
Fetal Brain ◽  
In Utero ◽  
Near Term ◽  
Ovine Fetal

scholarly journals Thyroid hormones in fetal growth and prepartum maturation

2014 ◽  
Vol 221 (3) ◽  
pp. R87-R103 ◽  
Author(s):  
A J Forhead ◽  
A L Fowden
Keyword(s):  
Growth Factors ◽  
Thyroid Hormones ◽  
Fetal Growth ◽  
Growth And Development ◽  
Fetal Brain ◽  
Normal Growth ◽  
In Utero ◽  
Somatic Tissues ◽  
Near Term ◽  
Maternal Thyroid

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are essential for normal growth and development of the fetus. Their bioavailabilityin uterodepends on development of the fetal hypothalamic–pituitary–thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T4and T3concentrations are also affected by gestational age, nutritional and endocrine conditionsin utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating theprepartummaturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T4and T3bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.

Hypoxic regulation of the fetal cerebral circulation

2006 ◽  
Vol 100 (2) ◽  
pp. 731-738 ◽  
Author(s):  
William Pearce
Keyword(s):  
Cerebral Circulation ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Periventricular Leukomalacia ◽  
Cerebral Arteries ◽  
Fetal Brain ◽  
Respiratory Drive ◽  
Vascular Effect ◽  
Brain Structure And Function ◽  
And Function

Fetal cerebrovascular responses to acute hypoxia are fundamentally different from those observed in the adult cerebral circulation. The magnitude of hypoxic vasodilatation in the fetal brain increases with postnatal age although fetal cerebrovascular responses to acute hypoxia can be complicated by age-dependent depressions of blood pressure and ventilation. Acute hypoxia promotes adenosine release, which depresses fetal cerebral oxygen consumption through action of adenosine on neuronal A1 receptors and vasodilatation through activation of A2 receptors on cerebral arteries. The vascular effect of adenosine can account for approximately half the vasodilatation observed in response to hypoxia. Hypoxia-induced release of nitric oxide and opioids can account for much of the adenosine-independent cerebral vasodilatation observed in response to hypoxia in the fetus. Direct effects of hypoxia on cerebral arteries account for the remaining fraction, although the vascular endothelium contributes relatively little to hypoxic vasodilatation in the immature cerebral circulation. In contrast to acute hypoxia, fetal cerebral blood flow tends to normalize during acclimatization to chronic hypoxia even though cardiac output is depressed. However, uncompensated chronic hypoxia in the fetus can produce significant changes in brain structure and function, alteration of respiratory drive and fluid balance, and increased incidence of intracranial hemorrhage and periventricular leukomalacia. At the level of the fetal cerebral arteries, chronic hypoxia increases protein content and depresses norepinephrine release, contractility, and receptor densities associated with contraction but also attenuates endothelial vasodilator capacity and decreases the ability of ATP-sensitive and calcium-sensitive potassium channels to promote vasorelaxation. Overall, fetal cerebrovascular adaptations to chronic hypoxia appear prioritized to conserve energy while preserving basic contractility. Many gaps remain in our understanding of how the effects of acute and chronic hypoxia are mediated in fetal cerebral arteries, but studies of adult cerebral arteries have produced many powerful pharmacological and molecular tools that are simply awaiting application in studies of fetal cerebral artery responses to hypoxia.

scholarly journals Umbilical cord occlusions in near-term ovine fetus induce increased beat-to-beat heart rate variability correlating to decreases in neuroinflammation: a case for the afferent cholinergic anti-inflammatory pathway?

2015 ◽  
Author(s):  
Martin G Frasch ◽  
Mark Szynkaruk ◽  
Andrew P Prout ◽  
Karen Nygard ◽  
Ruud Veldhuizen ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Vagus Nerve ◽  
Fetal Brain ◽  
In Utero ◽  
Inflammatory Pathway ◽  
Anti Inflammatory ◽  
Near Term ◽  
Ovine Fetal

Neuroinflammation in utero may contribute to brain injury resulting in life long neurological disabilities. The pivotal role of the efferent cholinergic anti-inflammatory pathway (CAP) in controlling inflammation has been described in adults, but its importance in the fetus is unknown. Moreover, it is unknown whether CAP may also exert anti-inflammatory effects on the brain via CAP's afferent component of the vagus nerve. Based on multiple clinical studies in adults and our own work in fetal autonomic nervous system, we gauged the degree of CAP activity in vivo using heart rate variability measures reflecting fluctuations in vagus nerve activity. Measuring microglial activation in the ovine fetal brain near-term, we show in vivo that afferent fetal CAP may translate increased vagal cholinergic signaling into suppression of cerebral inflammation in response to near-term hypoxic acidemia as might occur during labour. Our findings suggest a new control mechanism of fetal neuroinflammation via the vagus nerve, providing novel possibilities for its non-invasive monitoring in utero and for targeted treatment.

Intravenous angiotensin induces brain c-fos expression and vasopressin release in the near-term ovine fetus

2003 ◽  
Vol 285 (6) ◽  
pp. E1216-E1222 ◽  
Author(s):  
Lijun Shi ◽  
Fang Hu ◽  
Paul Morrissey ◽  
Jiaming Yao ◽  
Zhice Xu
Keyword(s):  
Intravenous Infusion ◽  
Fetal Brain ◽  
Circumventricular Organs ◽  
Ang Ii ◽  
Double Labeling ◽  
Vasopressin Release ◽  
Fetal Plasma ◽  
Ovine Fetus ◽  
Fos Expression ◽  
Near Term

The effect of intravenous angiotensin II (ANG II) on fetal brain c- fos expression and arginine vasopressin (AVP) release was studied in the near-term ovine fetus. Fetuses with chronically implanted catheters received an intravenous infusion of ANG II or saline. Fetal plasma AVP concentrations were significantly increased after the peripheral administration of ANG II, with peak levels (3-fold) at 30 min after the intravenous infusion. There was no change in fetal plasma osmolality, sodium, and hematocrit levels between the control and experimental groups or between the periods before and after the infusion of ANG II. Intravenous ANG II administration induced Fos immunoreactivity (Fos-IR) in the circumventricular organs and the median preoptic nucleus of the fetal brain. Fos-IR was also demonstrated in the fetal supraoptic nuclei (SON). Double labeling demonstrated that the AVP-containing neurons in the SON were expressing c- fos in response to intravenous ANG II. These results indicate that the peripheral ANG II in the fetus may play a significant role in stimulating the central hypothalamic-neurohypophysial system during late gestation. It supports the hypothesis that circulating ANG II may act at the fetal AVP neurons in the hypothalamus in body fluid balance via the circumventricular organs, which are situated outside the blood-brain barrier, and the central neural pathway between these two brain structures has been relatively established in utero, at least at near-term.

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