Impact of hypoxia-ischemia and dopamine treatment on dopamine receptor binding density in the preterm fetal sheep brain

2020 ◽  
Vol 129 (6) ◽  
pp. 1431-1438
Author(s):  
F. Y. Wong ◽  
A. Gogos ◽  
N. Hale ◽  
S. A. Ingelse ◽  
N. Brew ◽  
...  
Keyword(s):  
Cell Death ◽  
D2 Receptor ◽  
Human Infants ◽  
Fetal Sheep ◽  
D1 And D2 Receptors ◽  
Dopaminergic Pathway ◽  
Protein Expressions ◽  
Hypoxia Ischemia ◽  
Sheep Brain ◽  
Dopamine Receptor Binding

This is the first study on the effects of hypoxia-ischemia and dopamine treatment on the dopaminergic pathway in the preterm brain. In the striatum of fetal sheep (equivalent to ∼26–28 wk of human gestation), we demonstrate that hypoxia-ischemia leads to cell death, reduces D1 and D2 receptors, and reduces dopamine transporter. Intravenous dopamine infusion at clinical dosage used in preterm human infants does not alter the striatal cell death, D1 and D2 receptor density levels, and DAT protein expressions after hypoxia-ischemia in the preterm brain.

scholarly journals Moderately Inducing Autophagy Reduces Tertiary Brain Injury after Perinatal Hypoxia-Ischemia

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 898
Author(s):  
Brian H. Kim ◽  
Maciej Jeziorek ◽  
Hur Dolunay Kanal ◽  
Viorica Raluca Contu ◽  
Radek Dobrowolski ◽  
...  
Keyword(s):  
Cell Death ◽  
Structural Integrity ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Brain Slices ◽  
Brain Structures ◽  
Improved Outcomes ◽  
Hypoxia Ischemia ◽  
Tgfβ Receptor ◽  
Progressive Neurodegeneration

Recent studies of cerebral hypoxia-ischemia (HI) have highlighted slowly progressive neurodegeneration whose mechanisms remain elusive, but if blocked, could considerably improve long-term neurological function. We previously established that the cytokine transforming growth factor (TGF)β1 is highly elevated following HI and that delivering an antagonist for TGFβ receptor activin-like kinase 5 (ALK5)—SB505124—three days after injury in a rat model of moderate pre-term HI significantly preserved the structural integrity of the thalamus and hippocampus as well as neurological functions associated with those brain structures. To elucidate the mechanism whereby ALK5 inhibition reduces cell death, we assessed levels of autophagy markers in neurons and found that SB505124 increased numbers of autophagosomes and levels of lipidated light chain 3 (LC3), a key protein known to mediate autophagy. However, those studies did not determine whether (1) SB was acting directly on the CNS and (2) whether directly inducing autophagy could decrease cell death and improve outcome. Here we show that administering an ALK5 antagonist three days after HI reduced actively apoptotic cells by ~90% when assessed one week after injury. Ex vivo studies using the lysosomal inhibitor chloroquine confirmed that SB505124 enhanced autophagy flux in the injured hemisphere, with a significant accumulation of the autophagic proteins LC3 and p62 in SB505124 + chloroquine treated brain slices. We independently activated autophagy using the stimulatory peptide Tat-Beclin1 to determine if enhanced autophagy is directly responsible for improved outcomes. Administering Tat-Beclin1 starting three days after injury preserved the structural integrity of the hippocampus and thalamus with improved sensorimotor function. These data support the conclusion that intervening at this phase of injury represents a window of opportunity where stimulating autophagy is beneficial.

Intercellular barriers to and transcellular transfer of albumin in the fetal sheep brain

1997 ◽  
Vol 195 (3) ◽  
pp. 229-236 ◽  
Author(s):  
Y. Balslev ◽  
K. M. Dziegielewska ◽  
K. Møllgård ◽  
N. R. Saunders
Keyword(s):  
Fetal Sheep ◽  
Sheep Brain

scholarly journals Effect of Zishenpingchan Granule on Neurobehavioral Manifestations and the Activity and Gene Expression of Striatal Dopamine D1 and D2 Receptors of Rats with Levodopa-Induced Dyskinesias

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Qing Ye ◽  
Xiao-Lei Yuan ◽  
Jie Zhou ◽  
Can-xing Yuan ◽  
Xu-ming Yang
Keyword(s):  
Gene Expression ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
D2 Receptors ◽  
Striatal Dopamine ◽  
Control Group ◽  
Indirect Pathway ◽  
Dopamine D2 ◽  
D1 And D2 Receptors ◽  
Neurobehavioral Manifestations

This study was performed to observe the effects of Zishenpingchan granule on neurobehavioral manifestations and the activity and gene expression of striatal dopamine D1 and D2 receptors of rats with levodopa-induced dyskinesias (LID). We established normal control group, LID model group, and TCM intervention group. Each group received treatment for 4 weeks. Artificial neural network (ANN) was applied to excavate the main factor influencing variation in neurobehavioral manifestations of rats with LID. The results showed that overactivation in direct pathway mediated by dopamine D1 receptor and overinhibition in indirect pathway mediated by dopamine D2 receptor may be the main mechanism of LID. TCM increased the efficacy time of LD to ameliorate LID symptoms effectively mainly by upregulating dopamine D2 receptor gene expression.

Repeated isoflurane exposure and neuroapoptosis in the midgestation fetal sheep brain

2016 ◽  
Vol 214 (4) ◽  
pp. 542.e1-542.e8 ◽  
Author(s):  
Olutoyin A. Olutoye ◽  
Fariha Sheikh ◽  
Irving J. Zamora ◽  
Ling Yu ◽  
Adesola C. Akinkuotu ◽  
...  
Keyword(s):  
Fetal Sheep ◽  
Sheep Brain

Effect of chronic hypoxemia on the regulation of nitric-oxide synthase in the fetal sheep brain

1998 ◽  
Vol 111 (2) ◽  
pp. 271-277 ◽  
Author(s):  
Kripamoy Aguan ◽  
Jun Murotsuki ◽  
Robert Gagnon ◽  
Loren P Thompson ◽  
Carl P Weiner
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Fetal Sheep ◽  
Sheep Brain ◽  
Chronic Hypoxemia ◽  
Oxide Synthase

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.

scholarly journals Connexin Hemichannel Mimetic Peptide Attenuates Cortical Interneuron Loss and Perineuronal Net Disruption Following Cerebral Ischemia in Near-Term Fetal Sheep

2020 ◽  
Vol 21 (18) ◽  
pp. 6475
Author(s):  
Panzao Yang ◽  
Joanne O. Davidson ◽  
Tania M. Fowke ◽  
Robert Galinsky ◽  
Guido Wassink ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Perineuronal Nets ◽  
Perinatal Hypoxia ◽  
Perineuronal Net ◽  
Fetal Sheep ◽  
Mimetic Peptide ◽  
Intracerebroventricular Infusion ◽  
Bilateral Carotid ◽  
Cortical Interneurons ◽  
Hypoxia Ischemia

Perinatal hypoxia-ischemia is associated with disruption of cortical gamma-aminobutyric acid (GABA)ergic interneurons and their surrounding perineuronal nets, which may contribute to persisting neurological deficits. Blockade of connexin43 hemichannels using a mimetic peptide can alleviate seizures and injury after hypoxia-ischemia. In this study, we tested the hypothesis that connexin43 hemichannel blockade improves the integrity of cortical interneurons and perineuronal nets. Term-equivalent fetal sheep received 30 min of bilateral carotid artery occlusion, recovery for 90 min, followed by a 25-h intracerebroventricular infusion of vehicle or a mimetic peptide that blocks connexin hemichannels or by a sham ischemia + vehicle infusion. Brain tissues were stained for interneuronal markers or perineuronal nets. Cerebral ischemia was associated with loss of cortical interneurons and perineuronal nets. The mimetic peptide infusion reduced loss of glutamic acid decarboxylase-, calretinin-, and parvalbumin-expressing interneurons and perineuronal nets. The interneuron and perineuronal net densities were negatively correlated with total seizure burden after ischemia. These data suggest that the opening of connexin43 hemichannels after perinatal hypoxia-ischemia causes loss of cortical interneurons and perineuronal nets and that this exacerbates seizures. Connexin43 hemichannel blockade may be an effective strategy to attenuate seizures and may improve long-term neurological outcomes after perinatal hypoxia-ischemia.

Cerebral metabolism in sheep: a comparative study of the adult, the lamb, and the fetus

1975 ◽  
Vol 229 (1) ◽  
pp. 235-239 ◽  
Author(s):  
Jones MD ◽  
LI Burd ◽  
EL Makowski ◽  
G Meschia ◽  
FC Battaglia
Keyword(s):  
Steady State ◽  
Comparative Study ◽  
Cerebral Metabolism ◽  
Lactate Production ◽  
Fetal Sheep ◽  
Sagittal Sinus ◽  
Sheep Brain ◽  
Beta Hydroxybutyrate ◽  
Arteriovenous Difference

The cerebral uptakes of glucose, oxygen, lactate, pyruvate, acetoacetate and beta-hydroxybutyrate were compared in the adult, the fetal, and the newborn sheep. Beginning 1-2 days after surgery, we withdrew samples simultaneously from an artery and from the sagittal sinus for up to 2 wk. At all ages glucose was the only substrate taken up in significant quantity relative to oxygen. The glucose-oxygen quotients were 0.98 less than 1.03 less than 1.08 in adults; 0.92 less than 0.99 less than 1.06 in lambs; 0.92 less than 0.98 less than 1.03 in fetuses. These quotients were not significantly different. There was a significant (P less than .05) arteriovenous difference for lactate in the adult (-0.031 mM), but not in the lamb or fetus. A significant (P less than .05) arteriovenous difference pyruvate was found in the adult (-0.013 mM) and in the fetus (-0.020 mM). The findings of a glucose-oxygen quotient of approximately 1 and the lack of significant lactate production in fetal sheep brain are consistent with the hypothesis that anerobic glycolysis is unimportant to the steady-state cerebral metabolism of the fetal sheep.

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