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erythropoietin neonatal brain

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https://www.readbyqxmd.com/read/29706928/repetitive-neonatal-erythropoietin-and-melatonin-combinatorial-treatment-provides-sustained-repair-of-functional-deficits-in-a-rat-model-of-cerebral-palsy
#1
Lauren L Jantzie, Akosua Y Oppong, Fatu S Conteh, Tracylyn R Yellowhair, Joshua Kim, Gabrielle Fink, Adam R Wolin, Frances J Northington, Shenandoah Robinson
Cerebral palsy (CP) is the leading cause of motor impairment for children worldwide and results from perinatal brain injury (PBI). To test novel therapeutics to mitigate deficits from PBI, we developed a rat model of extreme preterm birth (<28 weeks of gestation) that mimics dual intrauterine injury from placental underperfusion and chorioamnionitis. We hypothesized that a sustained postnatal treatment regimen that combines the endogenous neuroreparative agents erythropoietin (EPO) and melatonin (MLT) would mitigate molecular, sensorimotor, and cognitive abnormalities in adults rats following prenatal injury...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29514165/high-dose-erythropoietin-for-asphyxia-and-encephalopathy-heal-a-randomized-controlled-trial-background-aims-and-study-protocol
#2
Sandra E Juul, Bryan A Comstock, Patrick J Heagerty, Dennis E Mayock, Amy M Goodman, Stephanie Hauge, Fernando Gonzalez, Yvonne W Wu
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains an important cause of neonatal death and frequently leads to significant long-term disability in survivors. Therapeutic hypothermia, while beneficial, still leaves many treated infants with lifelong disabilities. Adjunctive therapies are needed, and erythropoietin (Epo) has the potential to provide additional neuroprotection. OBJECTIVES: The aim of this study was to review the current incidence, mechanism of injury, and sequelae of HIE, and to describe a new phase III randomized, placebo-controlled trial of Epo neuroprotection in term and near-term infants with moderate to severe HIE treated with therapeutic hypothermia...
March 7, 2018: Neonatology
https://www.readbyqxmd.com/read/29478510/plasma-biomarkers-of-brain-injury-in-neonatal-hypoxic-ischemic-encephalopathy
#3
An N Massaro, Yvonne W Wu, Theo K Bammler, Bryan Comstock, Amit Mathur, Robert C McKinstry, Taeun Chang, Dennis E Mayock, Sarah B Mulkey, Krisa Van Meurs, Sandra Juul
OBJECTIVES: To evaluate plasma brain specific proteins and cytokines as biomarkers of brain injury in newborns with hypoxic-ischemic encephalopathy (HIE) and, secondarily, to assess the effect of erythropoietin (Epo) treatment on the relationship between biomarkers and outcomes. STUDY DESIGN: A study of candidate brain injury biomarkers was conducted in the context of a phase II multicenter randomized trial evaluating Epo for neuroprotection in HIE. Plasma was collected at baseline (<24 hours) and on day 5...
March 2018: Journal of Pediatrics
https://www.readbyqxmd.com/read/29443550/erythropoietin-a-putative-neurotransmitter-during-hypoxia-is-produced-in-rvlm-neurons-and-activates-them-in-neonatal-wistar-rats
#4
Naoki Oshima, Hiroshi Onimaru, Akira Yamagata, Seigo Itoh, Hidehito Matsubara, Toshihiko Imakiire, Yasuhiro Nishida, Hiroo Kumagai
Recent studies indicate that erythropoietin (EPO) is present in many areas of the brain and is active in the restoration of impaired neurons. In this study, we examined the presence of EPO and its role in bulbospinal neurons in the rostral ventrolateral medulla (RVLM). Hypoxia is often accompanied by a high blood pressure (BP). We hypothesized that EPO is produced in response to hypoxia in RVLM neurons and then activates them. To investigate whether RVLM neurons are sensitive to EPO, we examined the changes in the membrane potentials (MPs) of bulbospinal RVLM neurons using the whole-cell patch-clamp technique during superfusion with EPO...
February 14, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29429559/epo-improved-neurologic-outcome-in-rat-pups-late-after-traumatic-brain-injury
#5
Michelle E Schober, Daniela F Requena, Christopher K Rodesch
In adult rats, erythropoietin improved outcomes early and late after traumatic brain injury, associated with increased levels of Brain Derived Neurotrophic Factor. Using our model of pediatric traumatic brain injury, controlled cortical impact in 17-day old rats, we previously showed that erythropoietin increased hippocampal neuronal fraction in the first two days after injury. Erythropoietin also decreased activation of caspase3, an apoptotic enzyme modulated by Brain Derived Neurotrophic Factor, and improved Novel Object Recognition testing 14 days after injury...
May 2018: Brain & Development
https://www.readbyqxmd.com/read/29335880/the-long-term-effect-of-erythropoiesis-stimulating-agents-given-to-preterm-infants-a-proton-magnetic-resonance-spectroscopy-study-on-neurometabolites-in-early-childhood
#6
Charles Gasparovic, Arvind Caprihan, Ronald A Yeo, John Phillips, Jean R Lowe, Richard Campbell, Robin K Ohls
BACKGROUND: Erythropoiesis stimulating agents (ESAs) are neuroprotective in cell and animal models of preterm birth. Prematurity has been shown to alter neurometabolite levels in children in studies using proton magnetic resonance spectroscopy (1H-MRS). OBJECTIVE: We hypothesized that ESA treatment in premature infants would tend to normalize neurometabolites by 4-6 years of age. MATERIALS AND METHODS: Children in a longitudinal study of neurodevelopment underwent MRI and 1H-MRS at approximately 4 years and 6 years of age...
March 2018: Pediatric Radiology
https://www.readbyqxmd.com/read/29288070/neonatal-erythropoietin-mitigates-impaired-gait-social-interaction-and-diffusion-tensor-imaging-abnormalities-in-a-rat-model-of-prenatal-brain-injury
#7
Shenandoah Robinson, Christopher J Corbett, Jesse L Winer, Lindsay A S Chan, Jessie R Maxwell, Christopher V Anstine, Tracylyn R Yellowhair, Nicholas A Andrews, Yirong Yang, Laurel O Sillerud, Lauren L Jantzie
Children who are born preterm are at risk for encephalopathy of prematurity, a leading cause of cerebral palsy, cognitive delay and behavioral disorders. Current interventions are limited and none have been shown to reverse cognitive and behavioral impairments, a primary determinant of poor quality of life for these children. Moreover, the mechanisms of perinatal brain injury that result in functional deficits and imaging abnormalities in the mature brain are poorly defined, limiting the potential to target interventions to those who may benefit most...
April 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29077163/erythropoietin-reduces-hippocampus-injury-in-neonatal-rats-with-hypoxic-ischemic-brain-damage-via-targeting-matrix-metalloprotein-2
#8
L Zhang, L Wang, F-B Ning, T Wang, Y-C Liang, Y-L Liu
OBJECTIVE: Erythropoietin (EPO), as a type of the tissue-protective cytokines, is a 30.4 kDa hematopoietic glycoprotein. The purpose of this study was to explore the neuroprotective effects of EPO on the neonatal hypoxic-ischemic-induced hippocampus injury and the MMP-2 expression. MATERIALS AND METHODS: Neonatal Sprague-Dawley (SD) rats were randomly divided into an untreated group (control) and two hypoxia-ischemia (HI) groups treated with saline control or EPO...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28840056/effects-of-erythropoietin-on-gliogenesis-during-cerebral-ischemic-reperfusion-recovery-in-adult-mice
#9
Rongliang Wang, Jincheng Li, Yunxia Duan, Zhen Tao, Haiping Zhao, Yumin Luo
Erythropoietin (EPO) promotes oligodendrogenesis and attenuates white matter injury in neonatal rats. However, it is unknown whether this effect extends to adult mice and whether EPO regulate microglia polarization after ischemic stroke. Male adult C57BL/6 mice (25-30g) were subjected to 45 min of middle cerebral artery occlusion (MCAO). EPO (5000 IU/kg) or saline was injected intraperitoneally every other day after reperfusion. Neurological function was evaluated using the rotarod test at 1, 3, 7 and 14 days after MCAO...
July 2017: Aging and Disease
https://www.readbyqxmd.com/read/28511187/the-differential-effects-of-erythropoietin-exposure-to-oxidative-stress-on-microglia-and-astrocytes-in-vitro
#10
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
#11
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
#12
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. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), caspase-3 and brain derived neurotrophic factor (BDNF) mRNA study and histopathological study were performed...
November 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
#13
RANDOMIZED CONTROLLED TRIAL
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.
July 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28445874/erythropoietin-treatment-exacerbates-moderate-injury-after-hypoxia-ischemia-in-neonatal-superoxide-dismutase-transgenic-mice
#14
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
#15
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
#16
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
#17
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
#18
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
#19
RANDOMIZED CONTROLLED TRIAL
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...
May 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
#20
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
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