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Neonatal brain injury

Raghavendra Rao, Motaz Nashawaty, Saher Fatima, Kathleen Ennis, Ivan Tkac
Hyperglycemia (blood glucose concentration >150 mg/dL) is common in extremely low gestational age newborns (ELGANs; birth at <28 week gestation). Hyperglycemia increases the risk of brain injury in the neonatal period. The long-term effects are not well understood. In adult rats, hyperglycemia alters hippocampal energy metabolism. The effects of hyperglycemia on the developing hippocampus were studied in rat pups. In Experiment 1, recurrent hyperglycemia of graded severity (moderate hyperglycemia (moderate-HG), mean blood glucose 214...
March 13, 2018: NMR in Biomedicine
Juan Zhang, Lorelei Donovan Tucker, DongYan, Yujiao Lu, Luodan Yang, Chongyun Wu, Yong Li, Quanguang Zhang
Hypoxic-ischemic (HI) encephalopathy is a leading cause of dire mortality and morbidity in neonates. Unfortunately, no effective therapies have been developed as of yet. Oxidative stress plays a critical role in pathogenesis and progression of neonatal HI. Previously, as a Nrf2 activator, tert-butylhydroquinone (TBHQ) has been demonstrated to exert neuroprotection on brain trauma and ischemic stroke models, as well as oxidative stress-induced cytotoxicity in neurons. It is, however, still unknown whether TBHQ administration can protect against oxidative stress in neonatal HI brain injury...
March 9, 2018: Neurochemistry International
Shan Yang, You-Chen Zhang, Hui-Wen Li, Zheng-Yong Jin
OBJECTIVE: To investigate the protective effect of prostaglandin E1 (PGE-1) against brain injury induced by hyperoxia in neonatal rats and observe the changes in the expression of glucose-regulated protein 78 (GRP78) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and to provide a theoretical basis for the clinical application of PGE-1 in the treatment of neonatal brain injury induced by hyperoxia. METHODS: Sixty neonatal Wistar rats were randomly divided into air control group, hyperoxic brain injury model group, and hyperoxic brain injury+PGE-1 group...
March 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Lauren B Crawford, Meredith R Golomb
OBJECTIVE: Here we review the current literature regarding visual outcome after perinatal and childhood stroke. BACKGROUND: Visual deficits following stroke in adults are common and have been previously reviewed. Less is known about visual deficits following stroke in neonates and older children. Most of the literature regarding this subject has focused on preterm infants, or on other types of brain injury. This review summarizes the types of visual deficits seen in term infants following perinatal stroke and children following childhood stroke and predictors of outcome...
November 20, 2017: Pediatric Neurology
Heather Campbell, Rathinaswamy B Govindan, Srinivas Kota, Tareq Al-Shargabi, Marina Metzler, Nickie Andescavage, Taeun Chang, Gilbert Vezina, Adre du Plessis, An N Massaro
OBJECTIVE: To evaluate whether infants with hypoxic-ischemic encephalopathy and evidence of autonomic dysfunction have aberrant physiological responses to care events that could contribute to evolving brain injury. STUDY DESIGN: Continuous tracings of heart rate (HR), blood pressure (BP), cerebral near infrared spectroscopy, and video electroencephalogram data were recorded from newborn infants with hypoxic-ischemic encephalopathy who were treated with hypothermia...
March 6, 2018: Journal of Pediatrics
Jean-François Ghersi-Egea, Elodie Saudrais, Nathalie Strazielle
Drug bioavailability to the developing brain is a major concern in the treatment of neonates and infants as well as pregnant and breast-feeding women. Central adverse drug reactions can have dramatic consequences for brain development, leading to major neurological impairment. Factors setting the cerebral bioavailability of drugs include protein-unbound drug concentration in plasma, local cerebral blood flow, permeability across blood-brain interfaces, binding to neural cells, volume of cerebral fluid compartments, and cerebrospinal fluid secretion rate...
March 7, 2018: Pharmaceutical Research
Stephanie A Pasquesi, Susan S Margulies
Computational models are valuable tools for studying tissue-level mechanisms of traumatic brain injury, but to produce more accurate estimates of tissue deformation, these models must be validated against experimental data. In this study, we present in situ measurements of brain-skull displacement in the neonatal piglet head ( n  = 3) at the sagittal midline during six rapid non-impact rotations (two rotations per specimen) with peak angular velocities averaging 51.7 ± 1.4 rad/s. Marks on the sagittally cut brain and skull/rigid potting surfaces were tracked, and peak values of relative brain-skull displacement were extracted and found to be significantly less than values extracted from a previous axial plane model...
2018: Frontiers in Bioengineering and Biotechnology
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
Jie Gao, Ailin Luo, Jing Yan, Xi Fang, Xiaole Tang, Yilin Zhao, Shiyong Li
Accumulating evidence indicates that general anesthetics can cause acute neuroapoptosis and long-term cognitive deficit in models exposed to anesthetics during the brain growth-spurt period. Anesthetics-induced imbalance of mitochondrial fusion and fission preceded and contributed to developmental neuroapoptosis. Accordingly, the imbalance was accompanied by activation of dynamin-related protein (Drp)1 which was closely associated with synaptic degeneration in neurodegenerative diseases. Based on the neuroprotective role of mitochondrial division inhibitor-1 (mdivi-1) in neurodegeneration and stroke, we set out to examine whether mdivi-1 can mitigate developmental neurotoxicity induced by isoflurane...
2018: American Journal of Translational Research
Lilly L Chang, James L Wynn, Marisa J Pacella, Candace C Rossignol, Felix Banadera, Neil Alviedo, Alfonso Vargas, Jeffrey Bennett, Melissa Huene, Nicole Copenhaver, Livia Sura, Kimberly Barnette, Jayne Solomon, Nikolay A Bliznyuk, Josef Neu, Michael D Weiss
BACKGROUND: Withholding enteral feedings during hypothermia lacks supporting evidence. OBJECTIVES: We aimed to determine if minimal enteral nutrition (MEN) during hypothermia in patients with hypoxic-ischemic encephalopathy was associated with a reduced duration of parenteral nutrition, time to full oral feeds, and length of stay, but would not be associated with increased systemic inflammation or feeding complications. METHODS: We performed a pilot, retrospective, matched case-control study within the Florida Neonatal Neurologic Network from December 2012 to May 2016 of patients who received MEN during hypothermia (n = 17) versus those who were not fed (n = 17)...
March 6, 2018: Neonatology
Tao Xiong, Yi Qu, Huiqin Wang, Hongju Chen, Jianghu Zhu, Fengyan Zhao, Rong Zou, Li Zhang, Dezhi Mu
Glycogen synthase kinase 3 beta (GSK-3β) plays an important role in neurological outcomes after brain injury. However, its roles and mechanisms in hypoxia-ischemia (HI) are unclear. Activation of mTOR complex 1 (mTORC1) has been proven to induce the synthesis of proteins associated with regeneration. We hypothesized that GSK-3β inhibition could activate the mTORC1 signaling pathway, which may reduce axonal injury and induce synaptic protein synthesis and functional recovery of synapses after HI. By analyzing a P7 rat model of cerebral HI and an in vitro ischemic (oxygen glucose deprivation) model, we found that GSK-3β inhibitors (GSK-3β siRNA or lithium chloride) activated mTORC1 signaling, leading to increased expression of synaptic proteins, including synapsin 1, PSD95, and GluR1, and the microtubule-associated protein Tau and decreased expression of the axonal injury-associated protein amyloid precursor protein...
February 28, 2018: Journal of Neuropathology and Experimental Neurology
Qingyi Ma, Lubo Zhang
Neonatal hypoxia-ischemia (HI) is the most common cause of brain injury in neonates, which leads to high neonatal mortality and severe neurological morbidity in later life (Vannucci, 2000; Volpe, 2001). Yet the molecular mechanisms of neuronal death and brain damage induced by neonatal HI remain largely elusive. Herein, using both in vivo and in vitro models, we determine an endogenous neuroprotectant role of c-type natriuretic peptide (CNP) in preserving neuronal survival after HI brain injury in mouse pups...
March 5, 2018: Experimental Neurology
Qi Wen, Giulia M Muraca, Joseph Ting, Sarah Coad, Kenneth I Lim, Sarka Lisonkova
OBJECTIVE: Instrumental vaginal delivery is associated with birth trauma to infant and obstetric trauma to mother. As caesarean delivery rates increased during the past decades, the rate of instrumental vaginal delivery declined. We examined concomitant temporal changes in the rates of severe birth trauma and maternal obstetric trauma. DESIGN: A retrospective observational study. SETTINGS AND PARTICIPANTS: All hospital singleton live births in Washington State, USA, 2004-2013, excluding breech delivery...
March 2, 2018: BMJ Open
M A Olude, S T Bello, O A Mustapha, F E Olopade, J Plendl, A O Ihunwo, J O Olopade
Oligodendrocyte and myelin-related studies have been pivotal in understanding disruption of central nervous system (CNS) myelin through injury, toxicological, pathological degeneration or genetic intervention. The African giant rat (AGR) has been postulated as an indigenous wild-type model within the African context. This work thus describes oligodendrocyte morphologies and myelin components of the developing African giant rat brain using histological, immunohistochemical and ultrastructural techniques. Five types, precursor-progenitor oligodendrocytes, pre-oligodendrocytes, immature oligodendrocytes, mature non-myelinating oligodendrocytes and mature myelinating oligodendrocytes, were identified...
March 1, 2018: Anatomia, Histologia, Embryologia
Annika C Linke, Conor Wild, Leire Zubiaurre-Elorza, Charlotte Herzmann, Hester Duffy, Victor K Han, David S C Lee, Rhodri Cusack
Objective: Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Methods: Infants ( n  = 65, included in final analyses: n  = 53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs...
2018: NeuroImage: Clinical
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
Molly Potter, Ted Rosenkrantz, R Holly Fitch
The current study investigated behavioral and post mortem neuroanatomical outcomes in Wistar rats with a neonatal hypoxic-ischemic (HI) brain injury induced on postnatal day 6 (P6; Rice-Vannucci HI method; Rice et al., 1981). This preparation models brain injury seen in premature infants (gestational age (GA) 32-35 weeks) based on shared neurodevelopmental markers at time of insult, coupled with similar neuropathologic sequelae (Rice et al., 1981; Workman et al., 2013). Clinically, HI insult during this window is associated with poor outcomes that include attention deficit hyperactivity disorder (ADHD), motor coordination deficits, spatial memory deficits, and language/learning disabilities...
February 21, 2018: International Journal of Developmental Neuroscience
Kiran S More, Pankaj Sakhuja, Regan E Giesinger, Joseph Y Ting, Matthew Keyzers, Jesal N Sheth, Anie Lapointe, Amish Jain, Aideen M Moore, Steven P Miller, Patrick J McNamara
OBJECTIVE:  This article compares hemodynamic characteristics of neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) with normal versus abnormal brain magnetic resonance imaging (MRI). METHODS:  Serial echocardiography (echo) was performed within 24 hours, after 48 to 72 hours of cooling, within 24 hours of normothermia, and after starting feeds. Pulmonary hemodynamics, cardiac output, and ventricular function were evaluated...
February 23, 2018: American Journal of Perinatology
Hans Jørgen Timm Guthe, Torbjørn Nedrebø, Jan Kristian Damås, Helge Wiig, Ansgar Berg
BACKGROUND: Therapeutic hypothermia is neuroprotective in asphyxiated neonates by counteracting mechanisms contributing to brain injury. Although an initial increased permeability is part of an inflammatory reaction and thereby a natural healing process, an excessive endothelial permeability with edema formation may result in impaired hemodynamics. Reduced permeability may, however, benefit healing. Although plasma and interstitial colloid osmotic pressure are accessible and essential parameters for understanding fluid imbalance, the mechanisms of fluid exchange remain poorly understood...
February 23, 2018: BMC Pediatrics
Anders Brunse, Päivi Worsøe, Susanne Elisabeth Pors, Kerstin Skovgaard, Per Torp Sangild
Preterm infants have increased risk of neonatal sepsis, potentially inducing brain injury, and they may benefit from early initiation of enteral milk feeding. Using preterm pigs as models, we hypothesized that early provision of bovine colostrum to parentally nourished newborns protects against sepsis and neuroinflammation during bloodstream infection. Preterm newborn pigs were administered 10 CFU/kg of intra-arterial Staphylococcus epidermidis (SE, an opportunistic pathogen often causing sepsis in preterm infants), followed by administration of total parenteral nutrition (TPN, SE + TPN, n = 15) or oral provision of bovine colostrum with supplementary parenteral nutrition (SE + COL, n = 14), and compared with uninfected, TPN-nourished controls (CON + TPN, n = 11)...
February 21, 2018: Shock
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