Cerebral haemodynamic response to somatosensory stimulation in near-term fetal sheep

Neurovascular coupling has been well-defined in the adult brain, but variable and inconsistent responses have been observed in the neonatal brain. The mechanisms that underlie functional haemodynamic responses in the developing brain are unknown. Synchrotron radiation (SR) microangiography enables in vivo high-resolution imaging of the cerebral vasculature. We exploited SR microangiography to investigate the microvascular changes underlying the cerebral haemodynamic response in preterm (n = 7) and 7–10-day old term lambs (n = 4), following median nerve stimulation of 1.8, 4.8 and 7.8 sec durations. Increasing durations of somatosensory stimulation significantly increased the number of cortical microvessels of ≤200 µm diameter in 7–10-day old term lambs (p < 0.05) but not preterm lambs where, in contrast, stimulation increased the diameter of cerebral microvessels with a baseline diameter of ≤200 µm. Preterm lambs demonstrated positive functional responses with increased oxyhaemoglobin measured by near infrared spectroscopy, while 7–10-day old term lambs demonstrated both positive and negative responses. Our findings suggest the vascular mechanisms underlying the functional haemodynamic response differ between the preterm and 7–10-day old term brain. The preterm brain depends on vasodilatation of microvessels without recruitment of additional vessels, suggesting a limited capacity to mount higher cerebral haemodynamic responses when faced with prolonged or stronger neural stimulation.

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Loss of interneurons and disruption of perineuronal nets in the cerebral cortex following hypoxia-ischaemia in near-term fetal sheep

Scientific Reports ◽

10.1038/s41598-018-36083-y ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 8

Author(s):

Tania M. Fowke ◽

Robert Galinsky ◽

Joanne O. Davidson ◽

Guido Wassink ◽

Rashika N. Karunasinghe ◽

...

Keyword(s):

Cerebral Cortex ◽

Perineuronal Nets ◽

Fetal Sheep ◽

Near Term

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Heat production of fetal sheep brain in utero

Journal of Applied Physiology ◽

10.1152/jappl.1977.43.4.747 ◽

1977 ◽

Vol 43 (4) ◽

pp. 747-749 ◽

Cited By ~ 3

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.

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Effect of Sildenafil on Pulmonary Circulation and Cardiovascular Function in Near-Term Fetal Sheep During Hypoxemia

Reproductive Sciences ◽

10.1177/1933719118773412 ◽

2018 ◽

Vol 26 (3) ◽

pp. 337-347 ◽

Cited By ~ 2

Author(s):

Amarnath Bhide ◽

Leena Alanne ◽

Juha Rasanen ◽

Heikki Huhta ◽

Juulia Junno ◽

...

Keyword(s):

Pulmonary Circulation ◽

Cardiovascular Function ◽

Fetal Sheep ◽

Near Term

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Peripheral chemoreflex activation and cardiac function during hypoxemia in near term fetal sheep without placental compromise

Journal of Applied Physiology ◽

10.1152/japplphysiol.01111.2020 ◽

2021 ◽

Author(s):

Juulia Lantto ◽

Tiina Erkinaro ◽

Mervi Haapsamo ◽

Heikki Huhta ◽

Leena Alanne ◽

...

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Carotid Artery ◽

Arterial Oxygen ◽

Sheep Model ◽

Fetal Sheep ◽

Descending Aorta ◽

Arterial Blood ◽

Near Term ◽

Peripheral Chemoreflex

A drop in arterial oxygen content activates fetal chemoreflex including an increase in sympathetic activity leading to peripheral vasoconstriction and redistribution of blood flow to protect the brain, myocardium, and adrenal glands. By using a chronically instrumented fetal sheep model with intact placental circulation at near-term gestation, we investigated the relationship between peripheral chemoreflex activation induced by hypoxemia and central hemodynamics. 17 Åland landrace sheep fetuses at 115-128/145 gestational days were instrumented. Carotid artery was catheterised in 10 fetuses and descending aorta in 7 fetuses. After a 4-day recovery, baseline measurements of fetal arterial blood pressures, blood gas values, and fetal cardiovascular hemodynamics by pulsed Doppler ultrasonography were obtained under isoflurane-anesthesia. Comparable data to baseline was collected 10 (acute hypoxemia) and 60 minutes (prolonged hypoxemia) after maternal hypo-oxygenation to saturation level of 70-80% was achieved. During prolonged hypoxemia, pH and base excess (BE) were lower, and lactate levels higher in the descending aorta than in the carotid artery. During hypoxemia mean arterial blood pressure (MAP) in the descending aorta increased, while in the carotid artery MAP decreased. In addition, right pulmonary artery pulsatility index values increased, and the diastolic component in the aortic isthmus blood flow velocity waveform became more retrograde. Both fetal ventricular cardiac outputs were maintained even during prolonged hypoxemia when significant fetal metabolic acidemia developed. Fetal chemoreflex activation induced by hypoxemia decreased the perfusion pressure in the cerebral circulation. Fetal weight-indexed LVCO or AoI Net Flow-ratio did not correlate with a drop in carotid artery blood pressure.

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Regulation of Ca2+sensitization by PKC and rho proteins in ovine cerebral arteries: effects of artery size and age

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.275.3.h930 ◽

1998 ◽

Vol 275 (3) ◽

pp. H930-H939 ◽

Cited By ~ 19

Author(s):

Sergey E. Akopov ◽

Lubo Zhang ◽

William J. Pearce

Keyword(s):

G Protein ◽

Cerebral Arteries ◽

Rho Kinase ◽

Cerebrovascular Reactivity ◽

Rho Proteins ◽

Experimental Conditions ◽

Fetal Sheep ◽

Middle Cerebral Arteries ◽

Near Term ◽

Nonpregnant Adult

G protein-regulated Ca2+ sensitivity of vascular contractile proteins plays an important role in cerebrovascular reactivity. The present study examines the intracellular mechanisms that govern G protein-regulated Ca2+ sensitivity in cerebral arteries of different size and age. We studied β-escin-permeabilized segments of common carotid, basilar, and middle cerebral arteries from nonpregnant adult and near-term fetal sheep. Activation of protein kinase C (PKC) by (−)-indolactam V or a phorbol ester produced receptor-independent increases in Ca2+ sensitivity. Such increases were more marked in immature arteries and were inversely correlated with artery size in both mature and immature arteries. However, inhibitors of PKC did not significantly affect increases in Ca2+ sensitivity in responses to either serotonin (5-hydroxytryptamine, 5-HT) or guanosine 5′- O-(3-thiotriphosphate) (GTPγS). Alternatively, deactivation of rho p21, a small G protein associated with Rho kinase, by exotoxin C3 fully prevented increases in Ca2+ sensitivity in responses to 5-HT or GTPγS in both adult and fetal arteries of all types. Neither inhibitors of PKC nor exotoxin C3 altered baseline Ca2+ sensitivity. We conclude that patterns of receptor- and/or G protein-mediated modulation of Ca2+ sensitivity are dependent on an intracellular pathway that involves activation of small G proteins and Rho kinase. In contrast, PKC has little, if any, role in agonist-induced Ca2+ sensitization under the present experimental conditions.

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Window of Opportunity of Cerebral Hypothermia for Postischemic White Matter Injury in the Near-Term Fetal Sheep

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/01.wcb.0000123904.17746.92 ◽

2004 ◽

Vol 24 (8) ◽

pp. 877-886 ◽

Cited By ~ 80

Author(s):

Vincent Roelfsema ◽

Laura Bennet ◽

Sherly George ◽

David Wu ◽

Jian Guan ◽

...

Keyword(s):

White Matter ◽

Cerebral Ischemia ◽

Caspase 3 ◽

Basic Protein ◽

White Matter Injury ◽

Window Of Opportunity ◽

Reactive Microglia ◽

Fetal Sheep ◽

Near Term ◽

Protein Density

Postresuscitation cerebral hypothermia is consistently neuroprotective in experimental preparations; however, its effects on white matter injury are poorly understood. Using a model of reversible cerebral ischemia in unanesthetized near-term fetal sheep, we examined the effects of cerebral hypothermia (fetal extradural temperature reduced from 39.4±0.1°C to between 30 and 33°C), induced at different times after reperfusion and continued for 72 hours after ischemia, on injury in the parasagittal white matter 5 days after ischemia. Cooling started within 90 minutes of reperfusion was associated with a significant increase in bioactive oligodendrocytes in the intragyral white matter compared with sham cooling (41±20 vs 18±11 per field, P < 0.05), increased myelin basic protein density and reduced expression of activated caspase-3 (14±12 vs 91±51, P < 0.05). Reactive microglia were profoundly suppressed compared with sham cooling (4±6 vs 38±18 per field, P < 0.05) with no effect on numbers of astrocytes. When cooling was delayed until 5.5 hours after reperfusion there was no significant effect on loss of oligodendrocytes (24±12 per field). In conclusion, hypothermia can effectively protect white matter after ischemia, but only if initiated early after the insult. Protection was closely associated with reduced expression of both activated caspase-3 and of reactive microglia.

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Effects of thyroid hormones on pulmonary and renal angiotensin-converting enzyme concentrations in fetal sheep near term

Journal of Endocrinology ◽

10.1677/joe.0.1730143 ◽

2002 ◽

Vol 173 (1) ◽

pp. 143-150 ◽

Cited By ~ 13

Author(s):

AJ Forhead ◽

AL Fowden

Keyword(s):

Angiotensin Converting Enzyme ◽

Thyroid Hormones ◽

Plasma Cortisol ◽

Experimental Manipulation ◽

Late Gestation ◽

Converting Enzyme ◽

Fetal Sheep ◽

Near Term ◽

Sheep Fetus

In the sheep fetus, pulmonary and renal concentrations of angiotensin-converting enzyme (ACE) increase towards term in parallel with the prepartum surges in plasma cortisol and tri-iodothyronine (T(3)). The ontogenic change in pulmonary ACE has been shown to be induced, at least in part, by cortisol but the role of the thyroid hormones is unknown. Therefore, this study investigated the effects of thyroid hormones on tissue ACE concentration in fetal sheep during late gestation. Pulmonary and renal ACE concentrations were measured in sheep fetuses after experimental manipulation of thyroid hormone status by fetal thyroidectomy and exogenous hormone infusion. In intact fetuses, pulmonary and renal ACE concentrations increased between 127-132 and 142-145 days of gestation (term 145 +/- 2 days), coincident with the prepartum rises in plasma cortisol and T(3). The ontogenic increment in pulmonary ACE concentration was abolished when the prepartum surge in T(3), but not cortisol, was prevented by fetal thyroidectomy. At 143-145 days, ACE concentration in the lungs and kidneys of the thyroidectomised fetuses were both lower than those in the intact fetuses. In intact fetuses at 127-132 days, pulmonary ACE was upregulated by intravenous infusions of either cortisol (2-3 mg/kg per day) or T(3) (8-12 microg/kg per day) for 5 days. Renal ACE was unaffected by cortisol or T(3) infusion. Therefore, thyroid hormones have an important role in the developmental control of pulmonary and renal ACE concentration in the sheep fetus towards term. In addition, the prepartum rise in plasma T(3) appears to mediate, in part, the maturational effect of cortisol on pulmonary ACE concentration.

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