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erythropoietin neonatal brain

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https://www.readbyqxmd.com/read/28511187/the-differential-effects-of-erythropoietin-exposure-to-oxidative-stress-on-microglia-and-astrocytes-in-vitro
#1
Praneeti Pathipati, Donna M Ferriero
The neonatal brain is especially susceptible to oxidative stress owing to its reduced antioxidant capacity. Following hypoxic-ischemic (HI) injury, for example, there is a prolonged elevation in levels of hydrogen peroxide (H2O2) in the immature brain compared to the adult brain, resulting in lasting injury that can lead to life-long disability or morbidity. Erythropoietin (Epo) is one of few multifaceted treatment options that have been promising enough to trial in the clinic for both term and preterm brain injury...
2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28486224/long-term-neuropathological-changes-associated-with-cerebral-palsy-in-a-nonhuman-primate-model-of-hypoxic-ischemic-encephalopathy
#2
Ryan M McAdams, Bobbi Fleiss, Christopher Traudt, Leslie Schwendimann, Jessica M Snyder, Robin L Haynes, Niranjana Natarajan, Pierre Gressens, Sandra E Juul
BACKGROUND: Cerebral palsy (CP) is the most common motor disability in childhood, with a worldwide prevalence of 1.5-4/1,000 live births. Hypoxic-ischemic encephalopathy (HIE) contributes to the burden of CP, but the long-term neuropathological findings of this association remain limited. METHODOLOGY: Thirty-four term Macaca nemestrina macaques were included in this long-term neuropathological study: 9 control animals delivered by cesarean section and 25 animals with perinatal asphyxia delivered by cesarean section after 15-18 min of umbilical cord occlusion (UCO)...
2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28472013/reoxygenation-with-100-oxygen-following-hypoxia-in-mice-causes-apoptosis
#3
Yoshiro Nishimura, Masaaki Ueki, Masaki Imanishi, Shuhei Tomita, Masaki Ueno, Jun Morishita, Takashi Nishiyama
After hypoxia, reoxygenation with air is the consensus treatment for full-term neonates; however, the effect of hyperoxic reoxygenation of adults is unknown. The present study was designed to investigate the effects of reoxygenation with 100% oxygen after hypoxia on inflammation and apoptosis in mice. Eight-week-old mice were either subjected to hypoxia in 8% oxygen for 30 min or air served as controls. Following hypoxia, mice underwent reoxygenation for 30 min with 21% or 100% oxygen. Tumour Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), caspase-3 and Brain Derived Neurotrophic Factor (BDNF) mRNA study and histopathological study were performed...
May 2, 2017: Shock
https://www.readbyqxmd.com/read/28456387/erythropoietin-and-brain-magnetic-resonance-imaging-findings-in-hypoxic-ischemic-encephalopathy-volume-of-acute-brain-injury-and-1-year-neurodevelopmental-outcome
#4
Sarah B Mulkey, Raghu H Ramakrishnaiah, Robert C McKinstry, Taeun Chang, Amit M Mathur, Dennis E Mayock, Krisa P Van Meurs, G Bradley Schaefer, Chunqiao Luo, Shasha Bai, Sandra E Juul, Yvonne W Wu
In the Neonatal Erythropoietin and Therapeutic Hypothermia Outcomes study, 9/20 erythropoietin-treated vs 12/24 placebo-treated infants with hypoxic-ischemic encephalopathy had acute brain injury. Among infants with acute brain injury, the injury volume was lower in the erythropoietin than the placebo group (P = .004). Higher injury volume correlated with lower 12-month neurodevelopmental scores. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01913340.
April 26, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28445874/erythropoietin-treatment-exacerbates-moderate-injury-after-hypoxia-ischemia-in-neonatal-superoxide-dismutase-transgenic-mice
#5
R Ann Sheldon, Christine Windsor, Byong Sop Lee, Olatz Arteaga Cabeza, Donna M Ferriero
The neonatal brain is highly susceptible to oxidative stress as developing endogenous antioxidant mechanisms are overwhelmed. In the neonate, superoxide dismutase (SOD) overexpression worsens hypoxic-ischemic injury due to H2O2 accumulation in the brain. Erythropoietin (EPO) is upregulated in 2 phases after HI, early (4 h) and late (7 days), and exogenous EPO has been effective in reducing the injury, possibly through reducing oxidative stress. We hypothesized that exogenous EPO would limit injury from excess H2O2 seen in SOD1-overexpressing mice, and thus enhance recovery after HI...
2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28359933/recombinant-human-erythropoietin-offers-neuroprotection-through-inducing-endogenous-erythropoietin-receptor-and-neuroglobin-in-a-neonatal-rat-model-of-periventricular-white-matter-damage
#6
Lihua Zhu, Li Huang, Quan Wen, Ting Wang, Lixing Qiao, Li Jiang
Recombinant human erythropoietin (rh-EPO) has been reported to have protective effects against brain injury. The purpose of this study was to evaluate the levels of erythropoietin receptor (EPOR) and neuroglobin (Ngb) in a neonatal rat model of periventricular white matter damage (PWMD), and to identify the relationship between the two proteins. On postnatal day 3 (P3), rats underwent permanent ligation of the right common carotid artery followed by 6% O2 for 4h (HI) or sham operation and normoxic exposure (sham)...
March 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28351056/comparison-of-umbilical-serum-copeptin-relative-to-erythropoietin-and-s100b-as-asphyxia-biomarkers-at-birth
#7
Milla Summanen, Laura Seikku, Petri Rahkonen, Vedran Stefanovic, Kari Teramo, Sture Andersson, Kai Kaila, Leena Rahkonen
BACKGROUND: Birth asphyxia, estimated to account for a million neonatal deaths annually, can cause a wide variety of neurodevelopmental impairments. There is a need to develop new, swift methods to identify those neonates who would benefit from neuroprotective treatments such as hypothermia. OBJECTIVES: To examine the utility of cord serum copeptin, a stable byproduct of arginine vasopressin release, as a biomarker of birth asphyxia based on a comparison with 2 biomarkers of hypoxia and brain trauma: erythropoietin and S100B...
2017: Neonatology
https://www.readbyqxmd.com/read/28346912/optimizing-the-dose-of-erythropoietin-required-to-prevent-acute-ventilation-induced-cerebral-white-matter-injury-in-preterm-lambs
#8
Kyra Y Y Chan, Domenic A LaRosa, Mary Tolcos, Anqi Li, Valerie A Zahra, Graeme R Polglase, Samantha K Barton
Erythropoietin (EPO) is being trialed in preterm neonates for neuroprotection. We have recently demonstrated that a single high bolus dose (5,000 IU/kg) of recombinant human EPO amplified preterm lung and brain ventilation-induced injury. We aimed to determine the optimal dose of EPO to reduce ventilation-induced cerebral white matter inflammation and injury in preterm lambs. Lambs (0.85 gestation) were ventilated with an injurious strategy for 15 min followed by conventional ventilation for 105 min. Lambs were randomized to no treatment (VENT; n = 8) or received a bolus dose of EPO (EPREX®): 300 IU/kg (EPO 300; n = 5), 1,000 IU/kg (EPO 1,000; n = 5), or 3,000 IU/kg (EPO 3,000; n = 5)...
2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28345550/recombinant-human-erythropoietin-augments-neovascularization-responses-in-a-neonatal-rat-model-of-premature-brain-damage-by-phosphatidylinositol-3-kinase-akt-pathway
#9
Da-Fan Yu, Li-Hua Zhu, Li Jiang
BACKGROUND: Recombinant human-erythropoietin (rh-EPO) has therapeutic efficacy for premature infants with brain damage during the active rehabilitation and anti-inflammation. In the present study, we found that the rh-EPO was related to the promotion of neovascularization. Our aim was to investigate whether rh-EPO augments neovascularization in the neonatal rat model of premature brain damage through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. METHODS: Postnatal day 5 (PD5), rats underwent permanent ligation of the right common carotid artery and were exposed to hypoxia for 2 h...
April 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28277490/erythropoietin-monotherapy-in-perinatal-asphyxia-with-moderate-to-severe-encephalopathy-a-randomized-placebo-controlled-trial
#10
R R Malla, R Asimi, M A Teli, F Shaheen, M A Bhat
OBJECTIVE: Erythropoietin (EPO) is neuroprotective after asphyxia in animal studies. The efficacy and safety of EPO monotherapy in term neonates with hypoxic ischemic encephalopathy (HIE) is uncertain. STUDY DESIGN: Hundred term neonates with moderate or severe HIE were randomized by random permuted block algorithm to receive either EPO 500 U kg(-1) per dose in 2 ml saline intravenously (50 neonates) on alternate days for a total of five doses with the first dose given by 6 h of age (treatment group) or 2 ml of normal saline (50 neonates) similarly for a total of five doses (placebo group) in a double-blind study...
March 9, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28041993/efficient-breathing-at-neonatal-ages-a-sex-and-epo-dependent-issue
#11
REVIEW
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
https://www.readbyqxmd.com/read/27995496/neuroprotective-effect-of-erythropoietin-on-phenylhydrazine-induced-hemolytic-hyperbilirubinemia-in-neonatal-rats
#12
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...
April 2017: Neurochemical Research
https://www.readbyqxmd.com/read/27902983/perinatal-asphyxia-and-erythropoietin-and-vegf-serial-serum-and-cerebrospinal-fluid-responses
#13
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...
2017: Neonatology
https://www.readbyqxmd.com/read/27887996/effects-of-erythropoietin-on-neonatal-hypoxia-ischemia-brain-injury-in-rat-model
#14
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
https://www.readbyqxmd.com/read/27830959/neonatal-hypoxic-ischemic-encephalopathy-an-update-on-disease-pathogenesis-and-treatment
#15
REVIEW
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...
May 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27718891/erythropoietin-reduces-white-matter-damage-in-two-day-old-rats-exposed-to-hypoxic-ischemia-injury
#16
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
https://www.readbyqxmd.com/read/27493706/erythropoietin-restores-long-term-neurocognitive-function-involving-mechanisms-of-neuronal-plasticity-in-a-model-of-hyperoxia-induced-preterm-brain-injury
#17
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
https://www.readbyqxmd.com/read/27244862/high-dose-erythropoietin-and-hypothermia-for-hypoxic-ischemic-encephalopathy-a-phase-ii-trial
#18
RANDOMIZED CONTROLLED TRIAL
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
https://www.readbyqxmd.com/read/27142685/delayed-erythropoietin-therapy-improves-histological-and-behavioral-outcomes-after-transient-neonatal-stroke
#19
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
https://www.readbyqxmd.com/read/27105430/ventilation-induced-brain-injury-in-preterm-neonates-a-review-of-potential-therapies
#20
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
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