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Hypoxic ischemia encephalopathy

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https://www.readbyqxmd.com/read/28703794/impaired-autophagosome-clearance-contributes-to-neuronal-death-in-a-piglet-model-of-neonatal-hypoxic-ischemic-encephalopathy
#1
Derong Cui, Dawei Sun, Xintao Wang, Liye Yi, Ewa Kulikowicz, Michael Reyes, Junchao Zhu, Zeng-Jin Yang, Wei Jiang, Raymond C Koehler
To examine the temporal relationship of cortical autophagic flux with delayed neuronal cell death after hypoxia-ischemia (HI) in neonatal piglets. HI was produced with 45-min hypoxia and 7-min airway occlusion in 3-5-day-old piglets. Markers of autophagic, lysosomal and cell death signaling were studied via immunohistochemistry, immunoblotting, and histochemistry in piglet brains. In vitro, autophagy was impaired in cultured mouse cortical neurons treated with chloroquine with or without rapamycin for 1 d in the presence of Z-VAD-fmk, cyclosporine A, or vehicle control, and cell viability was assessed with the MTT assay...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28599922/vitamin-d-improves-functional-outcomes-in-neonatal-hypoxic-ischemic-male-rats-treated-with-n-acetylcysteine-and-hypothermia
#2
Danielle W Lowe, Jamie L Fraser, Laura Grace Rollins, Jessica Bentzley, Xingju Nie, Renee Martin, Inderjit Singh, Dorothea Jenkins
Hypothermia treatment neuroprotects approximately 50% of neonates who present with moderate to severe hypoxic ischemic encephalopathy (HIE). N-acetylcysteine (NAC), a potent antioxidant, is neuroprotective in combination with hypothermia in neonatal hypoxia-ischemia (HI) female rats, but less protective in males. Vitamin D is a neurosteroid, which may provide immunomodulation and improve outcomes for both sexes. We investigated the efficacy of this combination of drugs with hypothermia after severe HI, as well as potential mechanisms of vitamin D effects in the transition to chronic inflammation...
June 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28576310/the-paracrine-effect-of-cobalt-chloride-on-bmscs-during-cognitive-function-rescue-in-the-hibd-rat
#3
Ying Dai, Wendi Li, Min Zhong, Jie Chen, Qian Cheng, Youxue Liu, Tingyu Li
Hypoxia-ischemia (HI)-induced perinatal encephalopathy frequently causes chronic neurological morbidities and acute mortality. Bone mesenchymal stem cell (BMSC) transplantation could potentially promote functional and anatomical recovery of ischemic tissue. In vitro hypoxic preconditioning is an effective strategy to improve the survival of BMSCs in ischemic tissue. In this study, cobalt chloride (CoCl2) preconditioned medium from BMSC cultures was injected into the left lateral ventricle of HI rats using a micro-osmotic pump at a flow rate 1...
May 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28561815/effects-of-therapeutic-hypothermia-on-white-matter-injury-from-murine-neonatal-hypoxia-ischemia
#4
Elliot Koo, R Ann Sheldon, Byong Sop Lee, Zinaida S Vexler, Donna M Ferriero
BackgroundTherapeutic hypothermia (TH) is the standard of care for neonates with hypoxic-ischemic encephalopathy, but it is not fully protective in the clinical setting. Hypoxia-ischemia (HI) may cause white matter injury (WMI), leading to neurological and cognitive dysfunction.MethodsP9 mice were subjected to HI as previously described. Pups underwent 3.5 h of systemic hypothermia or normothermia. Cresyl violet and Perl's iron staining for histopathological scoring of brain sections was completed blindly on all brains...
May 31, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28504050/how-long-is-sufficient-for-optimal-neuroprotection-with-cerebral-cooling-after-ischemia-in-fetal-sheep
#5
Joanne O Davidson, Vittoria Draghi, Sean Whitham, Simerdeep K Dhillon, Guido Wassink, Laura Bennet, Alistair J Gunn
The optimal duration of mild "therapeutic" hypothermia for neonates with hypoxic-ischemic encephalopathy is surprisingly unclear. This study assessed the relative efficacy of cooling for 48 h versus 72 h. Fetal sheep (0.85 gestation) received sham ischemia (n = 9) or 30 min global cerebral ischemia followed by normothermia (n = 8) or delayed hypothermia from 3 h to 48 h (n = 8) or 72 h (n = 8). Ischemia was associated with profound loss of electroencephalogram (EEG) power, neurons in the cortex and hippocampus, and oligodendrocytes and myelin basic protein expression in the white matter, with increased Iba-1-positive microglia and proliferation...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28418828/a-comparison-of-blood-and-cerebrospinal-fluid-cytokines-il-1%C3%AE-il-6-il-18-tnf-%C3%AE-in-neonates-with-perinatal-hypoxia
#6
Darinka Šumanović-Glamuzina, Filip Čulo, Melanie Ivana Čulo, Paško Konjevoda, Marjana Jerković-Raguž
Perinatal hypoxia-ischemia is a specific and important pathological event in neonatal care practice. The data on relationship between the concentrations of cytokines in blood and cerebrospinal fluid (CSF) and perinatal brain injury are scarce. The aim of this study is to evaluate changes in interleukin (IL-1β, IL-6, and IL-18) and tumor necrosis factor alpha (TNF-α) levels in newborns with perinatal hypoxia (PNH). CSF and serum samples of 35 term and near-term (35-40 weeks) newborns with PNH, at the age of 3-96 hours, were analyzed using enzyme-linked immunosorbent assay...
April 18, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28395175/oxygen-and-oxidative-stress-in-the-perinatal-period
#7
REVIEW
Isabel Torres-Cuevas, Anna Parra-Llorca, Angel Sánchez-Illana, Antonio Nuñez-Ramiro, Julia Kuligowski, Consuelo Cháfer-Pericás, María Cernada, Justo Escobar, Máximo Vento
Fetal life evolves in a hypoxic environment. Changes in the oxygen content in utero caused by conditions such as pre-eclampsia or type I diabetes or by oxygen supplementation to the mother lead to increased free radical production and correlate with perinatal outcomes. In the fetal-to-neonatal transition asphyxia is characterized by intermittent periods of hypoxia ischemia that may evolve to hypoxic ischemic encephalopathy associated with neurocognitive, motor, and neurosensorial impairment. Free radicals generated upon reoxygenation may notably increase brain damage...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28250763/molecular-chaperones-and-hypoxic-ischemic-encephalopathy
#8
REVIEW
Cong Hua, Wei-Na Ju, Hang Jin, Xin Sun, Gang Zhao
Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway...
January 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28209514/plasma-metabolite-score-correlates-with-hypoxia-time-in-a-newly-born-piglet-model-for-asphyxia
#9
Julia Kuligowski, Rønnaug Solberg, Ángel Sánchez-Illana, Leonid Pankratov, Anna Parra-Llorca, Guillermo Quintás, Ola Didrik Saugstad, Máximo Vento
Hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia is a leading cause of mortality and acquired long-term neurologic co-morbidities in the neonate. The most successful intervention for the treatment of moderate to severe HIE is moderate whole body hypothermia initiated within 6h from birth. The objective and prompt identification of infants who are at risk of developing moderate to severe HIE in the critical first hours still remains a challenge. This work proposes a metabolite score calculated based on the relative intensities of three metabolites (choline, 6,8-dihydroxypurine and hypoxanthine) that showed maximum correlation with hypoxia time in a consolidated piglet model for neonatal hypoxia-ischemia...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28196356/therapeutic-hypothermia-provides-variable-protection-against-behavioral-deficits-after-neonatal-hypoxia-ischemia-a-potential-role-for-brain-derived-neurotrophic-factor
#10
Johana Diaz, Suleiman Abiola, Nancy Kim, Oliver Avaritt, Debra Flock, Jenny Yu, Frances J Northington, Raul Chavez-Valdez
BACKGROUND: Despite treatment with therapeutic hypothermia (TH), infants who survive hypoxic ischemic (HI) encephalopathy (HIE) have persistent neurological abnormalities at school age. Protection by TH against HI brain injury is variable in both humans and animal models. Our current preclinical model of hypoxia-ischemia (HI) and TH displays this variability of outcomes in neuropathological and neuroimaging end points with some sexual dimorphism. The detailed behavioral phenotype of this model is unknown...
2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28101531/osteopontin-is-a-blood-biomarker-for-microglial-activation-and-brain-injury-in-experimental-hypoxic-ischemic-encephalopathy
#11
Yikun Li, Eric B Dammer, Xiaohui Zhang-Brotzge, Scott Chen, Duc M Duong, Nicholas T Seyfried, Chia-Yi Kuan, Yu-Yo Sun
Clinical management of neonatal hypoxic-ischemic encephalopathy (HIE) suffers from the lack of reliable surrogate marker tests. Proteomic analysis may identify such biomarkers in blood, but there has been no proof-of-principle evidence to support this approach. Here we performed in-gel trypsin digestion of plasma proteins from four groups of 10-d-old mice [untouched and 24 h after low-dose lipopolysaccharide (LPS) exposure, hypoxia-ischemia (HI), or LPS/HI injury; n = 3 in each group) followed by liquid chromatography-tandem mass spectrometry and bioinformatics analysis to search for HI- and LPS/HI-associated brain injury biomarkers...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28099429/vitamin-d-insufficiency-in-neonatal-hypoxic-ischemic-encephalopathy
#12
Danielle W Lowe, Bruce W Hollis, Carol L Wagner, Thomas Bass, David A Kaufman, Michael J Horgan, Laurence M Givelichian, Koravangatta Sankaran, Jerome Y Yager, Lakshmi D Katikaneni, Don Wiest, Dorothea Jenkins
BACKGROUND: Vitamin D has neuroprotective and immunomodulatory properties, and deficiency is associated with worse stroke outcomes. Little is known about effects of hypoxia-ischemia or hypothermia treatment on vitamin D status in neonates with hypoxic-ischemic encephalopathy (HIE). We hypothesized vitamin D metabolism would be dysregulated in neonatal HIE altering specific cytokines involved in Th17 activation, which might be mitigated by hypothermia. METHODS: We analyzed short-term relationships between 25(OH) and 1,25(OH)2 vitamin D, vitamin D binding protein, and cytokines related to Th17 function in serum samples from a multicenter randomized controlled trial of hypothermia 33 (°)C for 48 h after HIE birth vs...
July 2017: Pediatric Research
https://www.readbyqxmd.com/read/28099423/high-dose-erythropoietin-population-pharmacokinetics-in-neonates-with-hypoxic-ischemic-encephalopathy-receiving-hypothermia
#13
Adam Frymoyer, Sandra E Juul, An N Massaro, Theo K Bammler, Yvonne W Wu
BACKGROUND: High-dose erythropoietin (Epo) is a promising neuroprotective treatment in neonates with hypoxic-ischemic encephalopathy (HIE) receiving hypothermia. We evaluated the pharmacokinetics and dose-exposure relationships of high-dose Epo in this population to inform future dosing strategies. METHODS: We performed a population pharmacokinetic analysis of 47 neonates with HIE treated with hypothermia who received up to six doses of Epo in two previous clinical trials...
June 2017: Pediatric Research
https://www.readbyqxmd.com/read/28062175/intranasal-c3a-treatment-ameliorates-cognitive-impairment-in-a-mouse-model-of-neonatal-hypoxic-ischemic-brain-injury
#14
Javier Morán, Anna Stokowska, Frederik R Walker, Carina Mallard, Henrik Hagberg, Marcela Pekna
Perinatal asphyxia-induced brain injury is often associated with irreversible neurological complications such as intellectual disability and cerebral palsy but available therapies are limited. Novel neuroprotective therapies as well as approaches stimulating neural plasticity mechanism that can compensate for cell death after hypoxia-ischemia (HI) are urgently needed. We previously reported that single i.c.v. injection of complement-derived peptide C3a 1h after HI induction prevented HI-induced cognitive impairment when mice were tested as adults...
April 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28011948/molecular-hydrogen-affords-neuroprotection-in-a-translational-piglet-model-of-hypoxic-ischemic-encephalopathy
#15
J Nemeth, V Toth-Szuki, V Varga, V Kovacs, G Remzso, F Domoki
Hypoxic-ischemic encephalopathy (HIE) is the major consequence of perinatal asphyxia (PA) in term neonates. Although the newborn piglet is an accepted large animal PA/HIE model, there is no consensus on PA-induction methodology to produce clinically relevant HIE. We aimed to create and to characterize a novel PA model faithfully reproducing all features of asphyxiation including severe hypercapnia resulting in HIE, and to test whether H2 is neuroprotective in this model. Piglets were anaesthetised, artificially ventilated, and intensively monitored (electroencephalography, core temperature, O2 saturation, arterial blood pressure and blood gases)...
October 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28002390/therapeutic-hypothermia-modulates-complement-factor-c3a-and-c5a-levels-in-a-rat-model-of-hypoxic-ischemic-encephalopathy
#16
Tushar A Shah, Jasmine E Nejad, Haree K Pallera, Frank A Lattanzio, Rawad Farhat, Parvathi S Kumar, Pamela S Hair, W Thomas Bass, Neel K Krishna
BACKGROUND: Therapeutic hypothermia (HT) is the only intervention that improves outcomes in neonatal hypoxic-ischemic encephalopathy (HIE). However, the multifactorial mechanisms by which HT impacts HIE are incompletely understood. The complement system plays a major role in the pathogenesis of ischemia-reperfusion injuries such as HIE. We have previously demonstrated that HT modulates complement activity in vitro. METHODS: Term equivalent rat pups were subjected to unilateral carotid ligation followed by hypoxia (8% O2) for 45 min to simulate HIE...
April 2017: Pediatric Research
https://www.readbyqxmd.com/read/27988510/in-the-era-of-therapeutic-hypothermia-how-well-do-studies-of-perinatal-neuroprotection-control-temperature
#17
Robert Galinsky, Justin M Dean, Christopher A Lear, Joanne O Davidson, Simerdeep Dhillon, Guido Wassink, Laura Bennet, Alistair J Gunn
In the era of therapeutic hypothermia, reliable preclinical studies are integral to successfully identify neuroprotective strategies to further improve outcomes of encephalopathy at term. We reviewed preclinical neuroprotection studies reported between January 2014 and June 2016 to assess the use of effective temperature monitoring and control. As a secondary measure, we examined whether studies addressed other methodological issues such as stage of brain development, sex differences, the timing of the treatment relative to the insult, and the histological and functional endpoints used after hypoxia-ischemia...
2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/27973415/oxidative-stress-in-hypoxic-ischemic-encephalopathy-molecular-mechanisms-and-therapeutic-strategies
#18
REVIEW
Mingyi Zhao, Ping Zhu, Masayuki Fujino, Jian Zhuang, Huiming Guo, IdrisAhmed Sheikh, Lingling Zhao, Xiao-Kang Li
Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of morbidity and mortality in neonates. Because of high concentrations of sensitive immature cells, metal-catalyzed free radicals, non-saturated fatty acids, and low concentrations of antioxidant enzymes, the brain requires high levels of oxygen supply and is, thus, extremely sensitive to hypoxia. Strong evidence indicates that oxidative stress plays an important role in pathogenesis and progression. Following hypoxia and ischemia, reactive oxygen species (ROS) production rapidly increases and overwhelms antioxidant defenses...
December 10, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27812521/preterm-hypoxic-ischemic-encephalopathy
#19
REVIEW
Krishna Revanna Gopagondanahalli, Jingang Li, Michael C Fahey, Rod W Hunt, Graham Jenkin, Suzanne L Miller, Atul Malhotra
Hypoxic-ischemic encephalopathy (HIE) is a recognizable and defined clinical syndrome in term infants that results from a severe or prolonged hypoxic-ischemic episode before or during birth. However, in the preterm infant, defining hypoxic-ischemic injury (HII), its clinical course, monitoring, and outcomes remains complex. Few studies examine preterm HIE, and these are heterogeneous, with variable inclusion criteria and outcomes reported. We examine the available evidence that implies that the incidence of hypoxic-ischemic insult in preterm infants is probably higher than recognized and follows a more complex clinical course, with higher rates of adverse neurological outcomes, compared to term infants...
2016: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/27750254/temporal-profile-of-circulating-micrornas-after-global-hypoxia-ischemia-in-newborn-piglets
#20
Håvard Tetlie Garberg, Marianne U Huun, Lars O Baumbusch, Monica Åsegg-Atneosen, Rønnaug Solberg, Ola Didrik Saugstad
BACKGROUND: There is a lack of reliable biomarkers that can identify and grade acute hypoxic-ischemic encephalopathy in newborns. MicroRNAs (miRNA) are short, non-coding strands of RNA that are released into the circulation in response to tissue stress and injury. Some miRNAs are highly tissue specific and thus may potentially be non-invasive biomarkers of neonatal hypoxic-ischemic brain injury. OBJECTIVE: The aim of this study was to characterize the temporal expression of selected circulating miRNAs in a clinically relevant piglet model of neonatal hypoxia-ischemia (HI)...
2017: Neonatology
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