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Hypoxic ischemia encephalopathy

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https://www.readbyqxmd.com/read/28250763/molecular-chaperones-and-hypoxic-ischemic-encephalopathy
#1
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
#2
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...
February 7, 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
#3
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...
February 15, 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
#4
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
#5
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(0)C for 48h after HIE birth versus normothermia in 50 infants with moderate to severe HIE...
January 18, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28099423/high-dose-erythropoietin-population-pharmacokinetics-in-neonates-with-hypoxic-ischemic-encephalopathy-receiving-hypothermia
#6
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 6 doses of Epo in two previous clinical trials...
January 18, 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
#7
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
#8
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
#9
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...
February 1, 2017: Pediatric Research
https://www.readbyqxmd.com/read/27988510/in-the-era-of-therapeutic-hypothermia-how-well-do-studies-of-perinatal-neuroprotection-control-temperature
#10
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...
December 17, 2016: Developmental Neuroscience
https://www.readbyqxmd.com/read/27973415/oxidative-stress-in-hypoxic-ischemic-encephalopathy-molecular-mechanisms-and-therapeutic-strategies
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27689921/diagnosis-of-vein-of-galen-aneurysmal-malformation-using-fetal-mri
#14
Li-Xia Zhou, Su-Zhen Dong, Ming-Feng Zhang
PURPOSE: To present three fetal vein of Galen aneurysmal malformations (VGAMs), which were diagnosed through magnetic resonance imaging (MRI), and highlight these cardiovascular findings. MATERIALS AND METHODS: We retrospectively reviewed three fetuses with VGAM at 31, 32, and 33 weeks of gestation. Feeding arteries and draining veins were observed by MRI. Secondary changes in the brain and high-output heart failure caused by high blood flow in the lesion were evaluated...
September 30, 2016: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/27659964/erythropoietin-improves-hypoxic-ischemic-encephalopathy-in-neonatal-rats-after-short-term-anoxia-by-enhancing-angiogenesis
#15
Fangfang Yan, Meimei Zhang, Yan Meng, Huijuan Li, Lie Yu, Xiaojie Fu, Youcai Tang, Chao Jiang
Erythropoietin (EPO) is important for angiogenesis after hypoxia/ischemia. In this study, we investigated whether recombinant human erythropoietin (rhEPO) can enhance angiogenesis, and promote cognitive function through vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway in a rat model of hypoxic-ischemic encephalopathy (HIE). RhEPO, selective VEGFR2 inhibitor (SU5416) or vehicle was administrated by intraperitoneal injection. The assessment for cognitive function begins on day 60 after anoxia...
November 15, 2016: Brain Research
https://www.readbyqxmd.com/read/27616300/neuroprotective-effects-of-hypothermia-in-inflammatory-sensitized-hypoxic-ischemic-encephalopathy
#16
Mathilde Chevin, Clémence Guiraut, Caroline Maurice-Gelinas, Jessica Deslauriers, Sylvain Grignon, Guillaume Sébire
BACKGROUND: Despite the recent introduction of hypothermia as a mandatory standard of care, the incidence of neonatal encephalopathy in full-term newborns and its devastating neuro-behavioral outcomes continues to be a major individual, familial and social issue. Neonatal encephalopathy is mainly due to the compounding and interacting effects of hypoxia-ischemia and inflammation resulting from placental and other perinatal infections. It is unclear why hypothermia is effective in alleviating neonatal encephalopathy in some, but not all, full-term newborns...
December 2016: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/27613478/amelioration-by-glycine-of-brain-damage-in-neonatal-rat-brain-following-hypoxia-ischemia
#17
Hiroko Mori, Ken Momosaki, Jun Kido, Tetsuo Naramura, Kenichi Tanaka, Shirou Matsumoto, Kimitoshi Nakamura, Hiroshi Mitsubuchi, Fumio Endo, Masanori Iwai
BACKGROUND: Glycine protected adult brains against injury in an experimental model of stroke, but, because the ischemic response of neonatal brains differs from that of adult brains, we examined the neuroprotective efficacy of glycine and associated mechanisms in an experimental model of neonatal hypoxic-ischemic (HI) encephalopathy. METHODS: Neonatal (postnatal day 7) Wistar rats were randomly divided into an untreated group (non-HI) and two HI groups that were treated with left common carotid artery ligation and saline control or glycine...
September 10, 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/27555552/sex-dependent-mitophagy-and-neuronal-death-following-rat-neonatal-hypoxia-ischemia
#18
T G Demarest, E L Waite, T Kristian, A C Puche, J Waddell, M C McKenna, G Fiskum
Males are more susceptible than females to long-term cognitive deficits following neonatal hypoxic-ischemic encephalopathy (HIE). Mitochondrial dysfunction is implicated in the pathophysiology of cerebral hypoxia-ischemia (HI), but the influence of sex on mitochondrial quality control (MQC) after HI is unknown. Therefore, we tested the hypothesis that mitophagy is sexually dimorphic and neuroprotective 20-24h following the Rice-Vannucci model of rat neonatal HI at postnatal day 7 (PN7). Mitochondrial and lysosomal morphology and degree of co-localization were determined by immunofluorescence in the cerebral cortex...
October 29, 2016: Neuroscience
https://www.readbyqxmd.com/read/27532878/protective-effects-of-transient-receptor-potential-canonical-channels-on-oxygen-glucose-deprivation-induced-cell-injury-in-neurons-and-pc12-cells
#19
Yan Wang, Yingbo Li, Chen Di, Tu Liu, Qianlin Hou, Shali Wang
Hypoxic-ischemic encephalopathy (HIE) is a serious clinical problem, responsible for many cases of motor impairment, cognitive deficits, and mortality. Transient receptor potential canonical (TRPC) channels are nonselective cation channels that play a role in many disorders, including trauma, pulmonary hypertension, and excitotoxicity. However, the properties and underlying mechanisms of TRPC channels in HIE are still controversial. Extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) are central signaling pathways that transmit signals from extracellular to intracellular agents and mediate prosurvival, proliferation, and motility proteins...
September 28, 2016: Neuroreport
https://www.readbyqxmd.com/read/27468695/pml-regulates-neuroprotective-innate-immunity-and-neuroblast-commitment-in-a-hypoxic-ischemic-encephalopathy-model
#20
Vuk Palibrk, Rajikala Suganthan, Katja Scheffler, Wei Wang, Magnar Bjørås, Stig Ove Bøe
Regulation of innate immune responses and activation of tissue regenerative processes are key elements in the pathophysiology of brain injuries. The promyelocytic leukemia (PML) gene was originally identified on a breakpoint of chromosomal translocation t(15;17) associated with acute PML. We have studied the role of PML protein during acute and regenerative phases after hypoxia-ischemia (HI) in brains of neonatal mice. We found that PML prevents tissue loss and apoptotic cell death selectively in subcortical regions of the brain at early stages after damage...
2016: Cell Death & Disease
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