scholarly journals Betamethasone effects on fetal sheep cerebral blood flow are not dependent on maturation of cerebrovascular system and pituitary-adrenal axis

2005 ◽  
Vol 564 (2) ◽  
pp. 575-588 ◽  
Author(s):  
Matthias Löhle ◽  
Thomas Müller ◽  
Carola Wicher ◽  
Marcus Roedel ◽  
Harald Schubert ◽  
...  
2007 ◽  
Vol 28 (5) ◽  
pp. 995-1008 ◽  
Author(s):  
Melissa M McClure ◽  
Art Riddle ◽  
Mario Manese ◽  
Ning Ling Luo ◽  
Dawn A Rorvik ◽  
...  

Periventricular white matter (PVWM) injury is the leading cause of neurologic disability in survivors of prematurity. To address the role of ischemia in PVWM and cerebral cortical injury, we hypothesized that immaturity of spatially distal vascular ‘end zones’ or ‘border zones’ predisposes PVWM to greater decreases in cerebral blood flow (CBF) than more proximal structures. We quantified regional CBF with fluorescently labeled microspheres in 0.65 gestation fetal sheep in histopathologically defined three-dimensional regions by post hoc digital dissection and coregistration algorithms. Basal flow in PVWM was significantly lower than in gyral white matter and cortex, but was equivalent in superficial, middle, and deep PVWM. Absolute and relative CBF (expressed as percentage of basal) did not differ significantly during ischemia or reperfusion between PVWM, gyral white matter, or cortex. Moreover, CBF during ischemia-reperfusion was equivalent in three adjacent PVWM levels and was not consistent with the magnitude of severity of PVWM injury, defined by TUNEL (terminal deoxynucleotidyltransferase-mediated dUPT nick end labeling) staining. However, the magnitude of ischemia was predicted by the severity of discrete cortical lesions. Hence, unlike cerebral cortex, unique CBF disturbances did not account for the distribution of PVWM injury. Previously defined cellular maturational factors, thus, appear to have a greater influence on PVWM vulnerability to ischemic injury than the presence of immature vascular boundary zones.


2004 ◽  
Vol 55 (4) ◽  
pp. 568-575 ◽  
Author(s):  
David Ley ◽  
Gylfi Oskarsson ◽  
Mikael Bellander ◽  
Edgar Hernandez-Andrade ◽  
Göran Lingman ◽  
...  

2014 ◽  
Vol 116 (3) ◽  
pp. 267-273 ◽  
Author(s):  
Rasmus Aamand ◽  
Yi-Ching Lynn Ho ◽  
Thomas Dalsgaard ◽  
Andreas Roepstorff ◽  
Torben E. Lund

The carbonic anhydrase (CA) inhibitor acetazolamide (AZ) is used routinely to estimate cerebrovascular reserve capacity in patients, as it reliably increases cerebral blood flow (CBF). However, the mechanism by which AZ accomplishes this CBF increase is not entirely understood. We recently discovered that CA can produce nitric oxide (NO) from nitrite, and that AZ enhances this NO production in vitro. In fact, this interaction between AZ and CA accounted for a large part of AZ's vasodilatory action, which fits well with the known vasodilatory potency of NO. The present study aimed to assess whether AZ acts similarly in vivo in the human cerebrovascular system. Hence, we increased or minimized the dietary intake of nitrate in 20 healthy male participants, showed them a full-field flickering dartboard, and measured their CBF response to this visual stimulus with arterial spin labeling. Doing so, we found a significant positive interaction between the dietary intake of nitrate and the CBF modulation afforded by AZ during visual stimulation. In addition, but contrary to studies conducted in elderly participants, we report no effect of nitrate intake on resting CBF in healthy human participants. The present study provides in vivo support for an enhancing effect of AZ on the NO production from nitrite catalyzed by CA in the cerebrovascular system. Furthermore, our results, in combination with the results of other groups, indicate that nitrate may have significant importance to vascular function when the cerebrovascular system is challenged by age or disease.


1995 ◽  
Vol 7 (3) ◽  
pp. 549 ◽  
Author(s):  
AJ Llanos ◽  
RA Riquelme ◽  
FA Moraga ◽  
G Cabello ◽  
JT Parer

The fetal llama exposed to an intense degree of hypoxaemia did not increase cerebral blood flow, but showed a marked peripheral vasoconstriction. The same cardiovascular response is observed in fetal sheep submitted to a extremely severe hypoxaemia, when the initial compensatory vasodilatory mechanisms in brain and heart fail. To investigate whether the fetal llama responses to acute hypoxaemia are adaptive, or whether they are the result of a breakdown of mechanisms of blood flow redistribution that favours the central nervous system, we studied seven fetal llamas (0.6-0.7 of gestation) chronically-catheterized during 1 h of graded and progressive hypoxaemia. Fetal ascending aorta blood gases and fetal cardiac output and its distribution (radiolabelled-microspheres) were measured after 60 min of normoxaemia (B) and at the end of 20 min (H20), 40 min (H40) and 60 min (H60) of hypoxaemia. Data were analysed by ANOVA and Newman-Keuls tests. Each treatment resulted in a lower (P < 0.05) percentage of haemoglobin saturation than hypoxaemia; H40 was lower than H20, and H60 was lower than H20 and H40. No statistical difference was observed among treatments for cardiac output or cerebral blood flow. These results demonstrate that fetal cardiac output and brain blood flow are maintained at all degrees of hypoxaemia, indicating that these cardiovascular responses are an adaptive response in the llama fetus, rather than an index of cardiorespiratory decompensation.


1990 ◽  
Vol 162 (1) ◽  
pp. 278-281 ◽  
Author(s):  
R.M. Abrams ◽  
J.C. Post ◽  
D.J. Burchfield ◽  
K.J. Gomez ◽  
A.A. Hutchison ◽  
...  

2002 ◽  
Vol 543 (3) ◽  
pp. 1015-1023 ◽  
Author(s):  
Arlin B. Blood ◽  
Christian J. Hunter ◽  
Gordon G. Power

1988 ◽  
Vol 119 (3) ◽  
pp. 389-395 ◽  
Author(s):  
A. N. Brooks ◽  
J. R. G. Challis

ABSTRACT To test the hypothesis that endogenous opioids participate in the regulation of the ontogenic development of the hypothalamic-pituitary-adrenal axis in fetal sheep, we measured changes in immunoreactive (ir) ACTH and cortisol concentrations in response to bolus injections of either the [Met]-enkephalin analogue, [d-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33-824; 25 μg), the opioid antagonist naloxone (1 mg), a combination of both, or saline vehicle, administered to chronically catheterized fetal sheep through late gestation. There were no effects of either FK 33-824, naloxone or saline on the release of ir-ACTH and cortisol at the earliest stage of gestation studied (days 110–115). By days 125–130, FK 33-824 caused a rapid but short-lived (30 min) increase in plasma ir-ACTH (P <0·05) which was accompanied by a smaller but nonsignificant increase in cortisol. Naloxone given concurrently with FK 33-824 abolished this response, thus providing evidence for a specific effect through opioid receptors. Naloxone given alone was without effect. At days 135–140, FK 33-824 caused a significant increase in ir-ACTH which was of similar duration and magnitude to that which occurred at days 125–130. There was a larger basal variation in plasma concentrations of cortisol than at days, 125–130, and a greater increase in cortisol after FK 33-824, although this did not reach statistical significance. Naloxone again reversed the effects of FK 33-824 but was without effect when given alone. We conclude that opioid receptors capable of mediating the effects of exogenously administered opioid peptides on the pituitary-adrenal axis are present in fetal sheep by days 123–130. However, we have been unable to demonstrate tonic control of this axis by endogenous opioids, since naloxone is ineffective when given alone. J. Endocr. (1988) 119, 389–395


1988 ◽  
Vol 66 (8) ◽  
pp. 1106-1112 ◽  
Author(s):  
A. N. Brooks ◽  
J. R. G. Challis

In sheep an increase in fetal pituitary–adrenal function, reflected in rising concentrations of plasma ACTH and cortisol, is important in relation to fetal organ maturation and the onset of parturition. This review presents evidence that implicates the hypothalamic–pituitary–adrenal axis in the control of parturition and describes recent experiments that explore in detail the maturation of the fetal hypothalamus and pituitary in relation to fetal adrenal function. Recent improvements for the measurement of ACTH in unextracted plasma and the ability to maintain vascular catheters in chronically catheterized fetal sheep have enabled subtle changes in fetal ACTH concentrations to be detected. As a result of these advances it has now been established that the terminal rise in cortisol, which is responsible for the onset of parturition in sheep, is preceded by an increase in fetal plasma ACTH concentrations. This has led to the hypothesis that birth results from the sequential development of the fetal hypothalamic–pituitary–adrenal axis with the signal originating from the fetal brain. This increase in trophic drive to the fetal adrenal may result from changes in the responsiveness of the fetal pituitary gland to factors that stimulate the release of ACTH. Corticotropin releasing factor (CRF) and arginine vasopressin are two such factors that stimulate the secretion of ACTH and cortisol secretion in the chronically catheterized fetal sheep. The response to these factors increases with gestational age and is sensitive to glucocorticoid feedback. Furthermore, repeated administration of CRF to immature fetal sheep results in pituitary and adrenal activation and in some cases may lead to premature parturition. Until recently, little was known of the controls of CRF secretion from the fetal hypothalamus. However, CRF has now been detected in the fetal sheep hypothalamus by radioimmunoassay and with immunohistochemistry, during the last third of pregnancy. The CRF material detected by radioimmunoassay co-elutes with synthetic ovine CRF on Sephadex G75 chromatography and also stimulates the release of ACTH from adult sheep pituitary cells maintained in culture. Furthermore at d100 of pregnancy (term of 145 days), CRF is released from fetal sheep hypothalami perifused in vitro both under basal conditions and in response to potassium-induced nerve terminal depolarization. Dexamethasone does not affect the release of CRF under these conditions. At d140, the hypothalamus contains similar quantities of immunoreactive and bioactive CRF which are released at a higher rate during in vitro perifusion. Potassium causes a similar release of CRF compared with d100 and again is unaffected by the presence of dexamethasone. However, at d140, dexamethasone does reduce basal CRF release. These results provide evidence for maturation of glucocorticoid feedback mechanisms at the level of the fetal hypothalamus and, together with the additional data presented in this review, illustrate the complexity of neuroendocrine control of the hypothalamic–pituitary–adrenal axis in birth.


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