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erythropoietin neonatal brain

Pablo Iturri, Aida Bairam, Jorge Soliz
During postnatal life, the respiratory control system undergoes intense development and is highly responsive to stimuli emerging from the environment. In fact, interruption of breathing prevents gas exchange and results in systemic hypoxia that, if prolonged, can lead to cardio-respiratory failure or sudden infant death. Moreover, in newborns and infants, respiratory disorders related to neural control dysfunction show significant sexual dimorphism with a higher prevalence in males. To this day, the therapeutic tools available to alleviate these respiratory disorders remain limited...
December 29, 2016: Respiratory Physiology & Neurobiology
Asli Memisoglu, Meltem Kolgazi, Akan Yaman, Elif Bahadir, Serap Sirvanci, Berrak Ç Yeğen, Eren Ozek
Neonatal unconjugated hyperbilirubinemia might cause severe bilirubin neurotoxicity in especially hemolytic conditions. The study aimed to elucidate the potential neuroprotective effects of erythropoietin (EPO) in hemolysis-induced hyperbilirubinemia. In newborn rats, hyperbilirubinemia secondary to hemolysis was induced by injecting with phenylhydrazine hydrochloride (PHZ) and rats were injected with either vehicle or EPO. At 54th hour of the PHZ injection, rats were decapitated. Serum levels of TNF-α, IL-1β, IL-10, brain-derived neurotrophic factor (BDNF) and S100-B and brain malondialdehyde, glutathione levels and myeloperoxidase activities were measured...
December 19, 2016: Neurochemical Research
Deirdre U Sweetman, Chike Onwuneme, William R Watson, John F A Murphy, Eleanor J Molloy
BACKGROUND: Infants with neonatal encephalopathy (NE) of hypoxic-ischaemic origin are at risk of oxidative and ischaemia-reperfusion injury, which may induce abnormal inflammatory responses involving excessive cytokine production and release in serum and cerebrospinal fluid (CSF). Systemic inflammation is found in infants with NE, and we therefore were interested in cytokines associated with hypoxia, including vascular endothelial growth factor (VEGF) and erythropoietin (Epo). OBJECTIVE: To investigate the relationship between Epo, VEGF levels, brain injury and outcome in a group of term infants exposed to perinatal asphyxia (PA) compared to controls...
December 1, 2016: Neonatology
Qing Ren, Zhong-Hui Jiang, Xing-Fang Zhang, Qiao-Zhi Yang
BACKGROUND: Hypoxic-ischemic (HI) injury to the developing brain remains a major cause of morbidity. To date, few therapeutic strategies could provide complete neuroprotection. Erythropoietin (EPO) has been shown to be beneficial in several models of neonatal HI. This study examines the effect of treatment with erythropoietin on postnatal day 2 (P2) rats introduced with HI injury. METHOD: Rats at P2 were randomized into four groups: sham, bilateral carotid artery occlusion (BCAO), BCAO + early EPO, and BCAO + late EPO groups...
February 1, 2017: Physiology & Behavior
Edibe Pembegül Yıldız, Barış Ekici, Burak Tatlı
Hypoxic ischemic encephalopathy (HIE) is the most important reason for morbidity and mortality in term-born infants. Understanding pathophysiology of the brain damage is essential for the early detection of patients with high risk for HIE and development of strategies for their treatments. Areas covered: This review discusses pathophysiology of the neonatal HIE and its treatment options, including hypothermia, melatonin, allopurinol, topiramate, erythropoietin, N-acetylcyctein, magnesium sulphate and xenon...
November 23, 2016: Expert Review of Neurotherapeutics
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...
February 26, 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
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