scholarly journals EEG sharp waves are a biomarker of striatal neuronal survival after hypoxia-ischemia in preterm fetal sheep

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Hamid Abbasi ◽  
Paul P. Drury ◽  
Christopher A. Lear ◽  
Alistair J. Gunn ◽  
Joanne O. Davidson ◽  
...  
Keyword(s):  
Neuronal Survival ◽  
Fetal Sheep ◽  
Sharp Waves ◽  
Hypoxia Ischemia

Robust Wavelet Stabilized ‘Footprints of Uncertainty’ for Fuzzy System Classifiers to Automatically Detect Sharp Waves in the EEG after Hypoxia Ischemia

2017 ◽  
Vol 27 (03) ◽  
pp. 1650051 ◽  
Author(s):  
Hamid Abbasi ◽  
Laura Bennet ◽  
Alistair J. Gunn ◽  
Charles P. Unsworth
Keyword(s):  
Sheep Model ◽  
Fetal Sheep ◽  
Large Variability ◽  
Sharp Wave ◽  
Sharp Waves ◽  
Hypoxia Ischemia ◽  
Footprint Of Uncertainty ◽  
Electroencephalogram Eeg ◽  
Logic System

Currently, there are no developed methods to detect sharp wave transients that exist in the latent phase after hypoxia-ischemia (HI) in the electroencephalogram (EEG) in order to determine if these micro-scale transients are potential biomarkers of HI. A major issue with sharp waves in the HI-EEG is that they possess a large variability in their sharp wave profile making it difficult to build a compact ‘footprint of uncertainty’ (FOU) required for ideal performance of a Type-2 fuzzy logic system (FLS) classifier. In this paper, we develop a novel computational EEG analysis method to robustly detect sharp waves using over 30[Formula: see text]h of post occlusion HI-EEG from an equivalent, in utero, preterm fetal sheep model cohort. We demonstrate that initial wavelet transform (WT) of the sharp waves stabilizes the variation in their profile and thus permits a highly compact FOU to be built, hence, optimizing the performance of a Type-2 FLS. We demonstrate that this method leads to higher overall performance of [Formula: see text] for the clinical [Formula: see text] sampled EEG and [Formula: see text] for the high resolution [Formula: see text] sampled EEG that is improved upon over conventional standard wavelet [Formula: see text] and [Formula: see text], respectively, and fuzzy approaches [Formula: see text] and [Formula: see text], respectively, when performed in isolation.

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.

scholarly journals Perinatal hypoxic-ischemic brain injury in large animal models: Relevance to human neonatal encephalopathy

2018 ◽  
Vol 38 (12) ◽  
pp. 2092-2111 ◽  
Author(s):  
Raymond C Koehler ◽  
Zeng-Jin Yang ◽  
Jennifer K Lee ◽  
Lee J Martin
Keyword(s):  
Brain Injury ◽  
Animal Models ◽  
Cerebral Hypoperfusion ◽  
Large Animal ◽  
Perinatal Hypoxia ◽  
Cellular Mechanisms ◽  
Fetal Sheep ◽  
Newborn Piglets ◽  
Large Animal Models ◽  
Hypoxia Ischemia

Perinatal hypoxia-ischemia resulting in death or lifelong disabilities remains a major clinical disorder. Neonatal models of hypoxia-ischemia in rodents have enhanced our understanding of cellular mechanisms of neural injury in developing brain, but have limitations in simulating the range, accuracy, and physiology of clinical hypoxia-ischemia and the relevant systems neuropathology that contribute to the human brain injury pattern. Large animal models of perinatal hypoxia-ischemia, such as partial or complete asphyxia at the time of delivery of fetal monkeys, umbilical cord occlusion and cerebral hypoperfusion at different stages of gestation in fetal sheep, and severe hypoxia and hypoperfusion in newborn piglets, have largely overcome these limitations. In monkey, complete asphyxia produces preferential injury to cerebellum and primary sensory nuclei in brainstem and thalamus, whereas partial asphyxia produces preferential injury to somatosensory and motor cortex, basal ganglia, and thalamus. Mid-gestational fetal sheep provide a valuable model for studying vulnerability of progenitor oligodendrocytes. Hypoxia followed by asphyxia in newborn piglets replicates the systems injury seen in term newborns. Efficacy of post-insult hypothermia in animal models led to the success of clinical trials in term human neonates. Large animal models are now being used to explore adjunct therapy to augment hypothermic neuroprotection.

scholarly journals Telomerase Reverse Transcriptase Upregulation Attenuates Astrocyte Proliferation and Promotes Neuronal Survival in the Hypoxic–Ischemic Rat Brain

Stroke ◽  
2011 ◽  
Vol 42 (12) ◽  
pp. 3542-3550 ◽  
Author(s):  
Yi Qu ◽  
Zhoujin Duan ◽  
Fengyan Zhao ◽  
Dapeng Wei ◽  
Jianbo Zhang ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Rat Brain ◽  
Neuronal Survival ◽  
Regulatory Protein ◽  
Neuronal Injury ◽  
Telomerase Reverse Transcriptase ◽  
Astrocyte Proliferation ◽  
Neurotrophin 3 ◽  
Hypoxia Ischemia ◽  
Developing Rat

Background and Purpose— Telomerase reverse transcriptase (TERT) is tightly related to the resistance of cells to stress and injury. However, little is known about the roles of TERT in the nervous system. We try to investigate the effects of TERT on the function of astrocytes in developing rat brains subjected to hypoxia–ischemia. Methods— TERT expression was detected in rat brains with hypoxia–ischemia. In in vitro study, the function of astrocytes with TERT overexpression was measured, and the effects of astrocyte on neuronal apoptosis were examined. Moreover, overexpression or inhibition of TERT was conducted in vivo by gene transduction. Astrocyte proliferation was examined through Ki67 staining. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining and brain infarct volume calculation were used to detect neuronal injury. Results— Both TERT mRNA and protein were upregulated in neurons within 2 days but shifted to astrocytes at Day 3 after hypoxia–ischemia. Astrocyte proliferation was inhibited with TERT overexpression due to the upregulation of cell-cycle regulatory protein p15. Meanwhile, the apoptosis of neurons increased, whereas neurons were cocultured with conditioned media from astrocytes with TERT inhibition compared with TERT overexpression due to the decrease of neurotrophin-3 expression in astrocytes. Furthermore, Ki67-positive astrocytes and neuronal injury were found to be inhibited in TERT-overexpressing rat brains with hypoxia–ischemia. Conclusions— TERT attenuates astrocyte proliferation and promotes neuronal survival in the developing rat brain after hypoxia–ischemia, partly through its enhancement of p15 and neurotrophin-3 expression in astrocytes.

scholarly journals Partial Neural Protection with Prophylactic Low-Dose Melatonin after Asphyxia in Preterm Fetal Sheep

2013 ◽  
Vol 34 (1) ◽  
pp. 126-135 ◽  
Author(s):  
Paul P Drury ◽  
Joanne O Davidson ◽  
Laura Bennet ◽  
Lindsea C Booth ◽  
Sidhartha Tan ◽  
...  
Keyword(s):  
White Matter ◽  
Microglial Activation ◽  
Low Dose ◽  
Neuronal Survival ◽  
Antioxidant Properties ◽  
Neuronal Loss ◽  
Limited Information ◽  
Melatonin Treatment ◽  
Fetal Sheep ◽  
Naturally Occurring

Melatonin is a naturally occurring indolamine with mild antioxidant properties that is neuroprotective in perinatal animals. There is limited information on its effects on preterm brain injury. In this study, 23 chronically instrumented fetal sheep received 25 minutes of complete umbilical cord occlusion at 101 to 104 days gestation (term is 147 days). Melatonin was administered to the ewe 15 minutes before occlusion (0.1 mg/kg bolus followed by 0.1 mg/kg per hour for 6 hours, n=8), or the equivalent volume of vehicle (2% ethanol, n=7), or saline ( n=8), or maternal saline plus sham occlusion ( n=8). Sheep were killed after 7 days recovery in utero. Fetal blood pressure, heart rate, nuchal activity, and temperature were similar between groups. Vehicle infusion was associated with improved neuronal survival in the caudate nucleus, but greater neuronal loss in the regions of the hippocampus, with reduced proliferation and increased ameboid microglia in the white matter ( P<0.05). Maternal melatonin infusion was associated with faster recovery of fetal EEG, prolonged reduction in carotid blood flow, similar neuronal survival to vehicle, improved numbers of mature oligodendrocytes, and reduced microglial activation in the white matter ( P<0.05). Prophylactic maternal melatonin treatment is partially protective but its effects may be partly confounded by ethanol used to dissolve melatonin.

Normobaric oxygen treatment improves neuronal survival functional recovery and axonal plasticity after newborn hypoxia-ischemia

2020 ◽  
Vol 379 ◽  
pp. 112338
Author(s):  
Taha Kelestemur ◽  
Mustafa C. Beker ◽  
Ahmet B. Caglayan ◽  
Berrak Caglayan ◽  
Serdar Altunay ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Neuronal Survival ◽  
Normobaric Oxygen ◽  
Axonal Plasticity ◽  
Oxygen Treatment ◽  
Hypoxia Ischemia

scholarly journals Effects of hypoxia-ischemia and inotropes on expression of cardiac adrenoceptors in the preterm fetal sheep

2018 ◽  
Vol 125 (5) ◽  
pp. 1368-1377 ◽  
Author(s):  
Dana S. Hutchinson ◽  
Nadine Brew ◽  
Teresa Vu ◽  
Jon Merlin ◽  
Nadia Hale ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Prolonged Exposure ◽  
Inadequate Response ◽  
Mrna Levels ◽  
Adrenergic Agonists ◽  
Inotropic Therapy ◽  
Fetal Sheep ◽  
Hypoxia Ischemia ◽  
Frequent Failure ◽  
Cardiac Adrenoceptors

Preterm infants frequently suffer cardiovascular compromise, with hypotension and/or low systemic blood flow, leading to tissue hypoxia-ischemia (HI). Many preterm infants respond inadequately to inotropic treatments using adrenergic agonists such as dobutamine (DB) or dopamine (DA). This may be because of altered cardiac adrenoceptor expression because of tissue HI or prolonged exposure to adrenergic agonists. We assessed the effects of severe HI with and without DB/DA treatment on cardiac adrenoceptor expression in preterm fetal sheep. Fetal sheep (93–95 days) exposed to sham surgery or severe HI induced by umbilical cord occlusion received intravenous DB or saline for 74 h (HI + DB, HI, Sham + DB, Sham). The HI groups were also compared with fetal sheep exposed to HI and DA. Fetal hearts were collected to determine β-adrenoceptor numbers using [125I]-cyanopindolol binding and mRNA expression of β1-, β2-, α1A-, α2A-, or α2B-adrenoceptors. The HI group had increased β-adrenoceptor numbers compared with all other groups in all four heart chambers ( P < 0.05). This increase in β-adrenoceptor numbers in the HI group was significantly reduced by DB infusion in all four heart chambers, but DA infusion in the HI group only reduced β-adrenoceptor numbers in the left atria and ventricle. DB alone did not affect β-adrenoceptor numbers in the sham animals. Changes in β1-adrenoceptor mRNA levels trended to parallel the binding results. We conclude that HI upregulates preterm fetal cardiac β-adrenoceptors, but prolonged exposure to adrenergic agonists downregulates adrenoceptors in the preterm heart exposed to HI and may underpin the frequent failure of inotropic therapy in preterm infants. NEW & NOTEWORTHY This is the first study, to our knowledge, on the effects of hypoxia-ischemia and adrenergic agonists on adrenoceptors in the preterm heart. In fetal sheep, we demonstrate that hypoxia-ischemia increases cardiac β-adrenoceptor numbers. However, exposure to both hypoxia-ischemia and adrenergic agonists (dobutamine or dopamine) reduces the increase in β-adrenoceptor numbers, which may underpin the inadequate response in human preterm infants to inotropic therapy using adrenergic agonists. Dobutamine alone does not affect the cardiac adrenoceptors in the sham animals.

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