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erythropoietin neonatal brain

Qing Ren, Xing-Fang Zhang, Jin-Ying Yang
OBJECTIVE: The aim of the study was to investigate whether erythropoietin (EPO) could protect against white matter damage (WMD) in a preterm equivalent neonatal rat hypoxic-ischemia (HI) model. METHODS: 113 two-day-old male rat pups were divided randomly into three groups: sham-treated, bilateral carotid artery occlusion (BCAO)-treated, BCAO + EPO-treated group. EPO (50 U/10 g body weight) or saline alone was administered intraperitoneally immediately after BCAO surgery...
October 8, 2016: Neurological Research
Daniela Hoeber, Marco Sifringer, Yohan van de Looij, Josephine Herz, Stéphane V Sizonenko, Karina Kempe, Meray Serdar, Joanna Palasz, Martin Hadamitzky, Stefanie Endesfelder, Joachim Fandrey, Ursula Felderhoff-Müser, Ivo Bendix
Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules...
2016: Oxidative Medicine and Cellular Longevity
Yvonne W Wu, Amit M Mathur, Taeun Chang, Robert C McKinstry, Sarah B Mulkey, Dennis E Mayock, Krisa P Van Meurs, Elizabeth E Rogers, Fernando F Gonzalez, Bryan A Comstock, Sandra E Juul, Michael E Msall, Sonia L Bonifacio, Hannah C Glass, An N Massaro, Lawrence Dong, Katherine W Tan, Patrick J Heagerty, Roberta A Ballard
OBJECTIVE: To determine if multiple doses of erythropoietin (Epo) administered with hypothermia improve neuroradiographic and short-term outcomes of newborns with hypoxic-ischemic encephalopathy. METHODS: In a phase II double-blinded, placebo-controlled trial, we randomized newborns to receive Epo (1000 U/kg intravenously; n = 24) or placebo (n = 26) at 1, 2, 3, 5, and 7 days of age. All infants had moderate/severe encephalopathy; perinatal depression (10 minute Apgar <5, pH <7...
June 2016: Pediatrics
Amara Larpthaveesarp, Margaret Georgevits, Donna M Ferriero, Fernando F Gonzalez
BACKGROUND AND PURPOSE: Stroke is a major cause of neonatal morbidity, often with delayed diagnosis and with no accepted therapeutic options. The purpose of this study is to investigate the efficacy of delayed initiation of multiple dose erythropoietin (EPO) therapy in improving histological and behavioral outcomes after early transient ischemic stroke. METHODS: 32 postnatal day 10 (P10) Sprague-Dawley rats underwent sham surgery or transient middle cerebral artery occlusion (tMCAO) for 3h, resulting in injury involving the striatum and parieto-temporal cortex...
September 2016: Neurobiology of Disease
Samantha K Barton, Mary Tolcos, Suzanne L Miller, Charles Christoph-Roehr, Georg M Schmölzer, Timothy J M Moss, Stuart B Hooper, Euan M Wallace, Graeme R Polglase
Mechanical ventilation is a risk factor for cerebral inflammation and brain injury in preterm neonates. The risk increases proportionally with the intensity of treatment. Recent studies have shown that cerebral inflammation and injury can be initiated in the delivery room. At present, initiation of intermittent positive pressure ventilation (IPPV) in the delivery room is one of the least controlled interventions a preterm infant will likely face. Varying pressures and volumes administered shortly after birth are sufficient to trigger pathways of ventilation-induced lung and brain injury...
2016: Neonatology
Hyun Ju Lee, Seong-Ho Koh, Ki-Min Song, In Joon Seol, Hyun-Kyung Park
BACKGROUND: The mTOR (mammalian target of rapamycin) signaling pathway is a master regulator of cell growth and proliferation in the nervous system. However, the effects of erythropoietin (EPO) treatment on the mTOR signaling pathway have not been elucidated in neonates with hypoxic/ischemic (H/I) brain injury. OBJECTIVES: We investigated the mechanism underlying the neuroprotective effect of EPO by analyzing the mTOR signaling pathway after H/I injury in a neonatal rat model...
2016: Neonatology
Kuo-Mao Lan, Lu-Tai Tien, Zhengwei Cai, Shuying Lin, Yi Pang, Sachiko Tanaka, Philip G Rhodes, Abhay J Bhatt, Renate D Savich, Lir-Wan Fan
The hematopoietic growth factor erythropoietin (EPO) has been shown to be neuroprotective against hypoxia-ischemia (HI) in Postnatal Day 7 (P7)-P10 or adult animal models. The current study was aimed to determine whether EPO also provides long-lasting neuroprotection against HI in P5 rats, which is relevant to immature human infants. Sprague-Dawley rats at P5 were subjected to right common carotid artery ligation followed by an exposure to 6% oxygen with balanced nitrogen for 1.5 h. Human recombinant EPO (rEPO, at a dose of 5 units/g) was administered intraperitoneally one hour before or immediately after insult, followed by additional injections at 24 and 48 h post-insult...
2016: International Journal of Molecular Sciences
Orlane Ballot, Sofien Laouafa, Elizabeth Elliot-Portal, Rose Tam, Nicolas Voituron, Vincent Joseph, Jorge Soliz
The stimulation of central chemoreceptors by CO2 is considered essential for breathing. The supporting evidence include the fact that central apnea in neonates correlates with immaturity of the CO2-sensing mechanism, and that congenital central hypoventilation syndrome (CCHS) is characterized by the absence of a ventilatory response to elevated PCO2. We reported previously that cerebral erythropoietin (Epo) is a potent respiratory stimulant upon normoxia and hypoxia. The injection of soluble Epo receptor (sEpoR; the natural EpoR competitor to bind Epo) via the cisterna magna (ICI: intra-cisternal injection) decreases basal ventilation in adult and newborn mice...
November 16, 2015: Neuroscience Letters
Shrena Patel, Robin K Ohls
Erythropoiesis-stimulating agents (ESAs) such as erythropoietin have been studied as red cell growth factors in preterm and term infants for more than 20 years. Recent studies have evaluated darbepoetin (Darbe, a long-acting ESA) for both erythropoietic effects and potential neuroprotection. We review clinical trials of Darbe in term and preterm infants, which have reported significant erythropoietic uses and neuroprotective effects. ESAs show great promise in decreasing or eliminating transfusions, and in preventing and treating brain injury in term and preterm infants...
September 2015: Clinics in Perinatology
Sandra E Juul, Gillian C Pet
Certain groups of neonates are at high risk of developing long-term neurodevelopmental impairment and might be considered candidates for neuroprotective interventions. This article explores some of these high-risk groups, relevant mechanisms of brain injury, and specific mechanisms of cellular injury and death. The potential of erythropoietin (Epo) to act as a neuroprotective agent for neonatal brain injury is discussed. Clinical trials of Epo neuroprotection in preterm and term infants are updated.
September 2015: Clinics in Perinatology
K Jane Hassell, Mojgan Ezzati, Daniel Alonso-Alconada, Derek J Hausenloy, Nicola J Robertson
Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear...
November 2015: Archives of Disease in Childhood. Fetal and Neonatal Edition
Junjie Lu, Li Jiang, Huan Zhu, Long Zhang, Ting Wang
In some regions of the hippocampus, neurogenesis persists throughout life and is upregulated following hypoxia/ischemia. The mechanisms underlying the upregulation of neurogenesis, however, are not known. Here we examined the expression of two factors thought to be involved in hypoxia-related neurogenesis, hypoxia-inducible factor-1α (HIF-1α) and brain-derived erythropoietin (EPO), in the hippocampus of neonatal rats following hypoxia-ischemia. Sprague-Dawley rat pups were exposed to hypoxia-ischemia conditions or hypoxia conditions only...
August 2014: Journal of Nanoscience and Nanotechnology
Katherine Louise Shea, Arvind Palanisamy
PURPOSE OF REVIEW: Hypoxic-ischemic brain injury is a leading cause of mortality and morbidity in neonates. Treating such injury by interrupting the excitotoxic-oxidative cascade is of immense importance. This review will focus on novel techniques of neuroprotection and describe the latest advances in established therapeutic methods. KEY FINDINGS: Although the primacy of therapeutic hypothermia in treating hypoxic-ischemic encephalopathy is well established, recent research establishes that the arbitrarily chosen regimen of cooling to 33°C for 72 h may indeed be the most appropriate method...
June 2015: Current Opinion in Anaesthesiology
Yvonne W Wu, Fernando F Gonzalez
Perinatal hypoxic-ischaemic encephalopathy (HIE) occurs in 1 to 3 per 1000 term births. HIE is not preventable in most cases, and therapies are limited. Hypothermia improves outcomes and is the current standard of care. Yet, clinical trials suggest that 44-53% of infants who receive hypothermia will die or suffer moderate to severe neurological disability. In this article, we review the preclinical and clinical evidence for erythropoietin (EPO) as a potential novel neuroprotective agent for the treatment of HIE...
April 2015: Developmental Medicine and Child Neurology
Steven J Korzeniewski, Elizabeth Allred, J Wells Logan, Raina N Fichorova, Stephen Engelke, Karl C K Kuban, T Michael O'Shea, Nigel Paneth, Mari Holm, Olaf Dammann, Alan Leviton
BACKGROUND: We sought to determine, in very preterm infants, whether elevated perinatal erythropoietin (EPO) concentrations are associated with increased risks of indicators of brain damage, and whether this risk differs by the co-occurrence or absence of intermittent or sustained systemic inflammation (ISSI). METHODS: Protein concentrations were measured in blood collected from 786 infants born before the 28th week of gestation. EPO was measured on postnatal day 14, and 25 inflammation-related proteins were measured weekly during the first 2 postnatal weeks...
2015: PloS One
R Ann Sheldon, Raha Sadjadi, Matthew Lam, Russell Fitzgerald, Donna M Ferriero
We have previously shown that glutathione peroxidase (GPx) overexpressing mice (hGPx-tg) have reduced brain injury after neonatal hypoxia-ischemia (HI) as a consequence of reduced hydrogen peroxide accumulation. However, this protection is reversed with hypoxia preconditioning, raising the question of the roles of the genes regulated by hypoxia-inducible factor-1α (HIF-1α) and their transcription products, such as erythropoietin (EPO), in both the initial protection and subsequent reversal of protection. hGPx-tg and their wild-type (WT) littermates underwent the Vannucci procedure of HI brain injury at postnatal day 9 - left carotid artery ligation followed by exposure to 10% oxygen for 50 min...
2015: Developmental Neuroscience
Pattaraporn T Chun, Ronald J McPherson, Luke C Marney, Sahar Z Zangeneh, Brendon A Parsons, Ali Shojaie, Robert E Synovec, Sandra E Juul
Biomarkers that indicate the severity of hypoxic-ischemic brain injury and response to treatment and that predict neurodevelopmental outcomes are urgently needed to improve the care of affected neonates. We hypothesize that sequentially obtained plasma metabolomes will provide indicators of brain injury and repair, allowing for the prediction of neurodevelopmental outcomes. A total of 33 Macaca nemestrina underwent 0, 15 or 18 min of in utero umbilical cord occlusion (UCO) to induce hypoxic-ischemic encephalopathy and were then delivered by hysterotomy, resuscitated and stabilized...
2015: Developmental Neuroscience
Rhonda Souvenir, Desislava Doycheva, John H Zhang, Jiping Tang
Recombinant human erythropoietin (rhEPO), over the past decade, was hailed as an auspicious therapeutic strategy for various types of brain injuries. The promising results from experiments conducted in animal models of stroke led to a hurried clinical trial that was swiftly aborted in Phase II. The multiple neuroprotective modalities of rhEPO failed to translate smoothly to human adult ischemic brain injury and provided limited aid to neonates. In light of the antithetical results, several questions were raised as to why and how this clinical trial failed...
2015: Current Medicinal Chemistry
Jieun Kim, In-Young Choi, Yafeng Dong, Wen-Tung Wang, William M Brooks, Carl P Weiner, Phil Lee
PURPOSE: To investigate the impact of chronic hypoxia on neonatal brains, and follow developmental alterations and adaptations noninvasively in a guinea pig model. Chronic hypoxemia is the prime cause of fetal brain injury and long-term sequelae such as neurodevelopmental compromise, seizures, and cerebral palsy. MATERIALS AND METHODS: Thirty guinea pigs underwent either normoxic and hypoxemic conditions during the critical stage of brain development (0.7 gestation) and studied prenatally (n = 16) or perinatally (n = 14)...
September 2015: Journal of Magnetic Resonance Imaging: JMRI
Laura L Lehman, Michael J Rivkin
BACKGROUND: Perinatal arterial ischemic stroke is as common as large vessel arterial ischemic stroke in adults and leads to significant morbidity. Perinatal arterial ischemic stroke is the most common identifiable cause of cerebral palsy and can lead to cognitive and behavioral difficulties that are amortized over a lifetime. METHODS: The literature on perinatal arterial ischemic stroke was reviewed and analyzed. RESULTS: Risk factors for perinatal arterial ischemic stroke include those that are maternal, neonatal, and placental...
December 2014: Pediatric Neurology
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